Cd28

Summary

Gene Symbol: Cd28
Description: CD28 antigen
Alias: T-cell-specific surface glycoprotein CD28
Species: mouse

Top Publications

  1. ncbi Identification and distribution of the costimulatory receptor CD28 in the mouse
    J A Gross
    Department of Molecular and Cell Biology, University of California, Berkeley 94720
    J Immunol 149:380-8. 1992
  2. pmc CD28-independent induction of T helper cells and immunoglobulin class switches requires costimulation by the heat-stable antigen
    Y Wu
    Michael Heidelberger Division of Immunology, Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York 10016, USA
    J Exp Med 187:1151-6. 1998
  3. ncbi CD28 and CTLA4 coordinately regulate airway inflammatory cell recruitment and T-helper cell differentiation after inhaled allergen
    J S Burr
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Am J Respir Cell Mol Biol 24:563-8. 2001
  4. pmc Dynamic equilibrium of B7-1 dimers and monomers differentially affects immunological synapse formation and T cell activation in response to TCR/CD28 stimulation
    Sumeena Bhatia
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 184:1821-8. 2010
  5. ncbi CD28/B7 system of T cell costimulation
    D J Lenschow
    Committee on Immunology, Ben May Institute, Chicago, Illinois 60637, USA
    Annu Rev Immunol 14:233-58. 1996
  6. ncbi CD80+Gr-1+ myeloid cells inhibit development of antifungal Th1 immunity in mice with candidiasis
    Antonella Mencacci
    Department of Experimental Medicine and Biochemical Science, University of Perugia, Perugia, Italy
    J Immunol 169:3180-90. 2002
  7. ncbi The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses
    Woong Kyung Suh
    Advanced Medical Discovery Institute, Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada
    Nat Immunol 4:899-906. 2003
  8. ncbi Memory CD8+ T cells require CD28 costimulation
    Annie B Borowski
    Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA
    J Immunol 179:6494-503. 2007
  9. ncbi B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse
    Tsvetelina Pentcheva-Hoang
    Department of Molecular and Cell Biology, Cancer Research Laboratory, Howard Hughes Medical Institute, University of California, Berkeley, 94720, USA
    Immunity 21:401-13. 2004
  10. pmc Preferential use of B7.2 and not B7.1 in priming of vaccinia virus-specific CD8 T cells
    Shahram Salek-Ardakani
    Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, San Diego, CA 92037, USA
    J Immunol 182:2909-18. 2009

Research Grants

Detail Information

Publications133 found, 100 shown here

  1. ncbi Identification and distribution of the costimulatory receptor CD28 in the mouse
    J A Gross
    Department of Molecular and Cell Biology, University of California, Berkeley 94720
    J Immunol 149:380-8. 1992
    ..On human T cells, it has been shown that antibodies to the Ag CD28 can provide a potent amplification signal for cytokine production and proliferation...
  2. pmc CD28-independent induction of T helper cells and immunoglobulin class switches requires costimulation by the heat-stable antigen
    Y Wu
    Michael Heidelberger Division of Immunology, Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York 10016, USA
    J Exp Med 187:1151-6. 1998
    It is well established that B7-CD28/CTLA4 interactions play an important role in the induction of T helper cells for T-dependent antibody responses...
  3. ncbi CD28 and CTLA4 coordinately regulate airway inflammatory cell recruitment and T-helper cell differentiation after inhaled allergen
    J S Burr
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Am J Respir Cell Mol Biol 24:563-8. 2001
    ..We examined how the balance of signals derived through the CD28 and cytotoxic T-lymphocyte antigen (CTLA) 4 receptors modulate the outcome of inhaled antigen exposure in a murine ..
  4. pmc Dynamic equilibrium of B7-1 dimers and monomers differentially affects immunological synapse formation and T cell activation in response to TCR/CD28 stimulation
    Sumeena Bhatia
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 184:1821-8. 2010
    ..We demonstrate that altering B7-1 to create a uniformly covalent dimeric state results in enhanced CD28-mediated formation of T cell-APC conjugates...
  5. ncbi CD28/B7 system of T cell costimulation
    D J Lenschow
    Committee on Immunology, Ben May Institute, Chicago, Illinois 60637, USA
    Annu Rev Immunol 14:233-58. 1996
    ..The CD28/B7 receptor/ligand system is one of the dominant costimulatory pathways...
  6. ncbi CD80+Gr-1+ myeloid cells inhibit development of antifungal Th1 immunity in mice with candidiasis
    Antonella Mencacci
    Department of Experimental Medicine and Biochemical Science, University of Perugia, Perugia, Italy
    J Immunol 169:3180-90. 2002
    ..PMN were found to inhibit the activation of IFN-gamma-producing CD4+ T cells and to induce apoptosis through a CD80/CD28-dependent mechanism...
  7. ncbi The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses
    Woong Kyung Suh
    Advanced Medical Discovery Institute, Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada
    Nat Immunol 4:899-906. 2003
    ..Thus, B7-H3 is a negative regulator that preferentially affects T(H)1 responses...
  8. ncbi Memory CD8+ T cells require CD28 costimulation
    Annie B Borowski
    Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA
    J Immunol 179:6494-503. 2007
    ..A current paradigm in immunology is that naive CD8(+) T cells require CD28 costimulation, whereas memory CD8(+) T cells do not...
  9. ncbi B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse
    Tsvetelina Pentcheva-Hoang
    Department of Molecular and Cell Biology, Cancer Research Laboratory, Howard Hughes Medical Institute, University of California, Berkeley, 94720, USA
    Immunity 21:401-13. 2004
    The reported affinity differences between CD28 and CTLA-4 binding to B7-1 and B7-2 may serve to selectively regulate CD28 and CTLA-4 function by differentially recruiting and/or stabilizing these molecules at the immunological synapse...
  10. pmc Preferential use of B7.2 and not B7.1 in priming of vaccinia virus-specific CD8 T cells
    Shahram Salek-Ardakani
    Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, San Diego, CA 92037, USA
    J Immunol 182:2909-18. 2009
    Recent studies have demonstrated that CD28 provides critical costimulatory signals required for optimal CD8 T cell expansion and effector function in response to several viruses, including influenza, HSV, and vaccinia virus (VACV)...
  11. ncbi Cd28 and Ctla-4, two related members of the Ig supergene family, are tightly linked on proximal mouse chromosome 1
    T A Howard
    Department of Medicine, Duke University Medical Center, Durham, NC 27705
    Immunogenetics 33:74-6. 1991
  12. ncbi Identification of intervals on chromosomes 1, 3, and 13 linked to the development of lupus in BXSB mice
    M E Haywood
    Imperial College School of Medicine, London, UK
    Arthritis Rheum 43:349-55. 2000
    ..To identify intervals containing systemic lupus erythematosus (SLE) susceptibility alleles in the BXSB strain of mice...
  13. pmc Induction of unresponsiveness and impaired T cell expansion by staphylococcal enterotoxin B in CD28-deficient mice
    H W Mittrucker
    Department of Immunology and Biophysics, Ontario Cancer Institute, University of Toronto, Ontario, Canada
    J Exp Med 183:2481-8. 1996
    We used CD28-deficient mice to analyze the importance of CD28 costimulation for the response against Staphylococcal enterotoxin B (SEB) in vivo. CD28 was necessary for the strong expansion of V beta 8+ T cells, but not for deletion...
  14. pmc A dose-dependent requirement for the proline motif of CD28 in cellular and humoral immunity revealed by a targeted knockin mutant
    Lindzy D Friend
    Program in Immunology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Exp Med 203:2121-33. 2006
    Activation of naive T cells requires the integration of signals through the antigen receptor and CD28. Although there is agreement on the importance of CD28, there remains controversy on the mechanism by which CD28 regulates T cell ..
  15. ncbi CD28 costimulation prevents cell death during primary T cell activation
    P J Noel
    Department of Medicine, University of Chicago, IL 60637, USA
    J Immunol 157:636-42. 1996
    b>CD28 has been demonstrated to play an important role in augmenting T cell proliferation and effector function. Costimulation through CD28 has also been reported to enhance human T cell survival...
  16. ncbi Requirements for B7-CD28 costimulation in mucosal IgA responses: paradoxes observed in CTLA4-H gamma 1 transgenic mice
    E Gärdby
    Department of Medical Microbiology and Immunology, University of Goteborg, Sweden
    J Immunol 161:49-59. 1998
    The block in the CD80/CD86-CD28/CTLA-4 pathway in CTLA4-H gamma 1 transgenic (Tg) mice results in strongly impaired systemic IgG immunity and failure to develop germinal center reactions...
  17. ncbi Acquisition of CD80 (B7-1) by T cells
    H Sabzevari
    Laboratory of Tumor Immunology and Biology, Division of Basic Sciences, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 166:2505-13. 2001
    ..Specificity of this acquisition was also shown by the lack of acquisition by T cells from CD28 knockout mice (implicating CD28 in this process), the lack of acquisition of CD40 (another molecule on the APC ..
  18. pmc B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4
    D A Mandelbrot
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 107:881-7. 2001
    To examine whether B7 costimulation can be mediated by a molecule on T cells that is neither CD28 nor CTLA4, we generated mice lacking both of these receptors...
  19. ncbi Differential T cell costimulatory requirements in CD28-deficient mice
    A Shahinian
    Department of Medical Biophysics and Immunology, University of Toronto, Canada
    Science 261:609-12. 1993
    ..It is thought that engagement of the CD28 molecule with its ligand B7 provides an essential costimulatory signal without which full activation of T cells ..
  20. pmc CD43 is a murine T cell costimulatory receptor that functions independently of CD28
    A I Sperling
    Ben May Institute, University of Chicago, Chicago, Illinois 60637, USA
    J Exp Med 182:139-46. 1995
    Costimulation mediated by the CD28 receptor has been shown to play an important role in the development of a vigorous T cell immune response. Nevertheless, CD28-deficient mice can mount effective T cell-dependent immune responses...
  21. ncbi Distinct signal transduction in mouse CD4+ and CD8+ splenic T cells after CD28 receptor ligation
    R Abe
    Immune Cell Biology Program, Naval Medical Research Institute, Bethesda, MD 20889
    J Immunol 154:985-97. 1995
    ..In the present report, using a newly generated mAb specific for CD28, signal transduction by the CD28 receptor has been studied in mouse splenic T cells...
  22. ncbi CTLA-4 can function as a negative regulator of T cell activation
    T L Walunas
    University of Chicago, Illinois 60637
    Immunity 1:405-13. 1994
    b>CD28 and CTLA-4 are related glycoproteins found on T cells. Ligation of CD28 following antigen receptor engagement provides a costimulatory signal required for T cell activation...
  23. ncbi CD28 is required for germinal center formation
    S E Ferguson
    Department of Medicine, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, IL 60637, USA
    J Immunol 156:4576-81. 1996
    Previous studies have demonstrated that the T cell costimulatory molecule, CD28, is important in the development of humoral immunity...
  24. pmc Protection against lethal toxic shock by targeted disruption of the CD28 gene
    B Saha
    Naval Medical Research Institute, Bethesda, Maryland 20889, USA
    J Exp Med 183:2675-80. 1996
    ..Here we report that CD28-deficient mice (CD28-/-) are completely resistant to TSST-1-induced lethal TSS while CD28 (+/-) littermate mice ..
  25. ncbi CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes
    D J Lenschow
    Ben May Institute for Cancer Research, Department of Pathology, University of Chicago, Illinois 60637, USA
    Immunity 5:285-93. 1996
    b>CD28 ligation delivers a costimulatory signal important in T cell activation...
  26. ncbi CD28 dependence of T cell differentiation to IL-4 production varies with the particular type 2 immune response
    W C Gause
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Immunol 158:4082-7. 1997
    ..The T cell surface molecule, CD28, is widely considered to be the principal costimulatory molecule involved in T cell differentiation to effector ..
  27. pmc Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes
    H Nishina
    Amgen Institute and Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, M5G 2C1 Toronto, Ontario, Canada
    J Exp Med 186:941-53. 1997
    ..kinase [ JNK] kinase) is a direct activator of stress-activated protein kinases ([SAPKs]/JNKs) in response to CD28 costimulation, CD40 signaling, or activation of the germinal center kinase...
  28. ncbi Timing and casting for actors of thymic negative selection
    N Dautigny
    Institut National de la Sante et de la Recherche Medicale, Unit 345, Institut Necker, Paris, France
    J Immunol 162:1294-302. 1999
    ..We confirm a role for CD40/CD40L interaction, and the absence of involvement of CD28 costimulation, in thymic deletion in vivo...
  29. ncbi Role of CD28 in the generation of effector and memory responses required for resistance to Toxoplasma gondii
    E N Villegas
    Department of Pathobiology, University of Pennsylvania, Philadelphia 19104, USA
    J Immunol 163:3344-53. 1999
    b>CD28 deficient (CD28-/-) mice were used to study the role of costimulation in the T cell-mediated, IFN-gamma-dependent mechanism of resistance to Toxoplasma gondii. These mice were resistant to infection with the ME49 strain of T. gondii...
  30. ncbi Analysis of 4-1BB ligand (4-1BBL)-deficient mice and of mice lacking both 4-1BBL and CD28 reveals a role for 4-1BBL in skin allograft rejection and in the cytotoxic T cell response to influenza virus
    M A DeBenedette
    Department of Immunology, University of Toronto, Ontario, Canada
    J Immunol 163:4833-41. 1999
    ..to 4-1BB (CD137) on activated CD4 and CD8 T cells and in conjunction with strong signals through the TCR provides a CD28-independent costimulatory signal leading to high level IL-2 production by primary resting T cells...
  31. ncbi A critical role for B7/CD28 costimulation in experimental autoimmune encephalomyelitis: a comparative study using costimulatory molecule-deficient mice and monoclonal antibody blockade
    A M Girvin
    Department of Microbiology Immunology, Northwestern University Medical School, Northwestern University Institute for Neuroscience, Chicago, IL 60611, USA
    J Immunol 164:136-43. 2000
    The B7/CD28 pathway provides critical costimulatory signals required for complete T cell activation and has served as a potential target for immunotherapeutic strategies designed to regulate autoimmune diseases...
  32. ncbi Structure of murine CTLA-4 and its role in modulating T cell responsiveness
    D A Ostrov
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Science 290:816-9. 2000
    ..of T cell responses is dependent on opposing signals transmitted through two related cell-surface receptors, CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)...
  33. ncbi Role of CD28-B7 interactions in generation and maintenance of CD8 T cell memory
    M Suresh
    Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Immunol 167:5565-73. 2001
    Although the role of CD28-B7 interaction in the activation of naive T cells is well established, its importance in the generation and maintenance of T cell memory is not well understood...
  34. ncbi Memory Th2 effector cells can develop in the absence of B7-1/B7-2, CD28 interactions, and effector Th cells after priming with an intestinal nematode parasite
    Melinda J Ekkens
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Immunol 168:6344-51. 2002
    ..However, few studies have examined the role of B7-1/B7-2/CD28 interactions in the development of a Th2 memory immune response...
  35. pmc CD28 plays a critical role in the segregation of PKC theta within the immunologic synapse
    Jianyong Huang
    Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 99:9369-73. 2002
    ..In this study, we investigated the functional involvement of CD28 costimulation in the T cell receptor (TCR)-mediated immunologic synapse formation with respect to protein kinase C (..
  36. ncbi A switch in costimulation from CD28 to 4-1BB during primary versus secondary CD8 T cell response to influenza in vivo
    Edward M Bertram
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    J Immunol 172:981-8. 2004
    ..In contrast, CD28(-/-) mice are defective in initial CD8 T cell expansion...
  37. ncbi Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation
    Pietro G Andres
    Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California 94143, USA
    Nat Immunol 5:435-42. 2004
    b>CD28 costimulation is essential for CD4(+) T cell proliferation, survival, interleukin 2 (IL-2) production and T helper type 2 development...
  38. ncbi Requirement for CD28 in the effector phase of allergic airway inflammation
    Stephanie L Kimzey
    Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    J Immunol 173:632-40. 2004
    ..This process requires the participation of the CD28 costimulatory receptor...
  39. ncbi CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2
    Xuguang Tai
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Immunol 6:152-62. 2005
    Efficient generation of regulatory T cells (T(reg) cells) in the thymus requires CD28 costimulation, but it is not known why...
  40. ncbi The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo
    Hisaya Akiba
    Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
    J Immunol 175:2340-8. 2005
    ICOS is a new member of the CD28 family of costimulatory molecules that is expressed on activated T cells. Its ligand B7RP-1 is constitutively expressed on B cells...
  41. ncbi Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells
    Alessio Delogu
    Research Institute of Molecular Pathology, Vienna Biocenter, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Immunity 24:269-81. 2006
    ..Pax5-repressed genes are also reexpressed in plasma cells, which depend for normal function on Cd28 and Ccr2 reactivation...
  42. pmc Modulation of NKT cell development by B7-CD28 interaction: an expanding horizon for costimulation
    Xincheng Zheng
    Department of Surgery, Comprehensive Cancer Center, Program of Molecular Mechanism of Diseases, University of Michigan, Ann Arbor, Michigan, United States of America
    PLoS ONE 3:e2703. 2008
    ..Here we show that in mice with targeted mutations of B7-1/2 and CD28, the TCRbeta(+)alpha-Galcer/CD1d(+) (iValpha14 NKT) subset is significantly reduced in the thymus, spleen and liver...
  43. pmc The kinase PDK1 integrates T cell antigen receptor and CD28 coreceptor signaling to induce NF-kappaB and activate T cells
    Sung Gyoo Park
    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nat Immunol 10:158-66. 2009
    In addition to ligation of the T cell antigen receptor (TCR), activation of the CD28 coreceptor by the costimulatory molecule B7 is required for induction of the transcription factor NF-kappaB and robust T cell activation, although the ..
  44. pmc CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance
    Randall H Friedline
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Exp Med 206:421-34. 2009
    ..These results demonstrate that CTLA-4 is absolutely required for FOXP3(+) regulatory T cell function in vivo...
  45. doi Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation
    Tadashi Yokosuka
    Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan
    Immunity 33:326-39. 2010
    T cell activation is positively and negatively regulated by a pair of costimulatory receptors, CD28 and CTLA-4, respectively...
  46. pmc Binding of superantigen toxins into the CD28 homodimer interface is essential for induction of cytokine genes that mediate lethal shock
    Gila Arad
    Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel Canada, Hebrew University Hadassah Medical School, Jerusalem, Israel
    PLoS Biol 9:e1001149. 2011
    ..b>CD28 is a homodimer expressed on T cells that functions as the principal costimulatory ligand in the immune response ..
  47. ncbi Absence of B7-dependent responses in CD28-deficient mice
    J M Green
    Department of Medicine, University of Chicago, Illinois 60637
    Immunity 1:501-8. 1994
    Costimulation of T cell proliferation can occur through the CD28 signal transduction pathway...
  48. ncbi Skin allograft rejection in CD28-deficient mice
    K Kawai
    Ontario Cancer Institute, Department of Medical Biophysics, University of Toronto, Canada
    Transplantation 61:352-5. 1996
    Costimulatory interactions between CD28 and the B7 family have been shown to augment T cell responses in general...
  49. ncbi Contribution of the CD28 molecule to allergic and irritant-induced skin reactions in CD28 -/- mice
    S Kondo
    Division of Dermatology, Sunnybrook Health Science Center, University of Toronto, Canada
    J Immunol 157:4822-9. 1996
    The CD28 molecule is thought to be essential for the costimulatory signals and is required for mitogenic activation of T cells...
  50. ncbi CD28 costimulation promotes the production of Th2 cytokines
    I C Rulifson
    Ben May Institute for Cancer Research, Department of Pathology, University of Chicago, IL 60637, USA
    J Immunol 158:658-65. 1997
    b>CD28 ligation augments TCR-mediated proliferation, IL-2 production, and T cell survival. However, the role of CD28 costimulation in T cell differentiation remains controversial...
  51. ncbi The roles of CD28 and CD40 ligand in T cell activation and tolerance
    K C Howland
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 164:4465-70. 2000
    Costimulation of T cell activation involves both the B7:CD28 as well as the CD40 ligand (CD40L):CD40 pathway...
  52. ncbi B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes
    B Salomon
    Committee on Immunology, Ben May Institute for Cancer Research and Department of Pathology, University of Chicago, Illinois 60637, USA
    Immunity 12:431-40. 2000
    b>CD28/B7 costimulation has been implicated in the induction and progression of autoimmune diseases...
  53. pmc Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4
    T Takahashi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 192:303-10. 2000
    ..b>CD28-deficient CD25(+)CD4(+) T cells can also suppress normal T cells, indicating that CD28 is dispensable for ..
  54. ncbi Role of CD28 for the generation and expansion of antigen-specific CD8(+) T lymphocytes during infection with Listeria monocytogenes
    H W Mittrucker
    Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
    J Immunol 167:5620-7. 2001
    ..We used CD28-deficient mice to characterize the function of CD28 during Listeria infection, with a main emphasis on Listeria-..
  55. ncbi Role of CD4 T cell help and costimulation in CD8 T cell responses during Listeria monocytogenes infection
    Devon J Shedlock
    Department of Microbiology, School of Medicine, University of Pennsylvania, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    J Immunol 170:2053-63. 2003
    ..The CD8 T cell response to L. monocytogenes was normal in CD40L(-/-) mice but defective in CD28(-/-) and CD137L(-/-) mice...
  56. pmc Mouse V alpha 14i natural killer T cells are resistant to cytokine polarization in vivo
    Jennifer L Matsuda
    La Jolla Institute for Allergy and Immunology, and Division of Biological Sciences, University of California, San Diego, CA, USA
    Proc Natl Acad Sci U S A 100:8395-400. 2003
    ....
  57. ncbi Physiologic and aberrant regulation of memory T-cell trafficking by the costimulatory molecule CD28
    Vincenzo Mirenda
    Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom
    Blood 109:2968-77. 2007
    ..The costimulatory molecule CD28 plays an essential role in the initiation of T-cell-mediated immunity...
  58. ncbi CD28 deficiency exacerbates joint inflammation upon Borrelia burgdorferi infection, resulting in the development of chronic Lyme arthritis
    Bettina P Iliopoulou
    Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA
    J Immunol 179:8076-82. 2007
    ..In this study, we report that the majority of Bb-infected CD28-/- mice develop chronic Lyme arthritis...
  59. pmc Control of memory CD8+ T cell differentiation by CD80/CD86-CD28 costimulation and restoration by IL-2 during the recall response
    Shinichiro Fuse
    Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA
    J Immunol 180:1148-57. 2008
    Memory CD8+ T cell responses have been considered to be independent of CD80/CD86-CD28 costimulation. However, recall responses are often severely blunted in CD28-/- mice...
  60. pmc Regulation of thymic NKT cell development by the B7-CD28 costimulatory pathway
    Joy A Williams
    Experimental Immunology Branch, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 181:907-17. 2008
    ..further the requirements for thymic iNKT cell development and find that these cells are highly sensitive to B7-CD28 costimulatory interactions, as evidenced by the substantially decreased numbers of thymic iNKT cells in CD28 and in ..
  61. doi Protection from graft-versus-host disease with a novel B7 binding site-specific mouse anti-mouse CD28 monoclonal antibody
    Niklas Beyersdorf
    Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, Germany
    Blood 112:4328-36. 2008
    We studied the role of CD28 in T-cell biology and T cell-mediated pathology using a novel mouse anti-mouse CD28 antibody, E18, which recognizes an epitope close to the B7 binding site...
  62. doi CD28 stimulation triggers NF-kappaB activation through the CARMA1-PKCtheta-Grb2/Gads axis
    Kei Takeda
    Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278 0022, Japan
    Int Immunol 20:1507-15. 2008
    b>CD28 stimulation contributes to activation of the IL-2 promoter by up-regulating the activity of several transcription factors, including nuclear factor kappaB (NF-kappaB)/Rel family members...
  63. pmc CD4(+)CD25(+) regulatory T cells resist a novel form of CD28- and Fas-dependent p53-induced T cell apoptosis
    Nagendra Singh
    Immunotherapy Center, Medical College of Georgia, Augusta, GA 30912, USA
    J Immunol 184:94-104. 2010
    ..When peripheral T cells were activated with anti-CD3 and anti-CD28 Abs precoated onto plastic plates, CD4(+)CD25(-) and CD8 T cells initially expanded but underwent massive apoptosis ..
  64. pmc Cutting edge: CD28 and c-Rel-dependent pathways initiate regulatory T cell development
    Kieng B Vang
    Department of Laboratory Medicine and Pathology, The Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
    J Immunol 184:4074-7. 2010
    ..The costimulatory molecule CD28 is required for efficient Treg development...
  65. doi AP-1 is involved in ICOS gene expression downstream of TCR/CD28 and cytokine receptor signaling
    Masashi Watanabe
    Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba, Japan
    Eur J Immunol 42:1850-62. 2012
    ..site (AP1-RE) within the ICOS promoter region and demonstrated AP-1 actually binds to AP1-RE upon TCR/CD28 stimulation...
  66. ncbi CD28-deficient mice generate an impaired Th2 response to Schistosoma mansoni infection
    C L King
    Division of Geographic Medicine, Case Western Reserve University, Cleveland, OH 44106 4983, USA
    Eur J Immunol 26:2448-55. 1996
    Engagement of CD28 on T cells provides a co-stimulatory signal necessary for T cell activation and differentiation. Recent findings suggest that priming of T helper (Th)2 cells is more dependent on CD28 activation that Th1 cells...
  67. pmc B7-1 engagement of cytotoxic T lymphocyte antigen 4 inhibits T cell activation in the absence of CD28
    F Fallarino
    Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA
    J Exp Med 188:205-10. 1998
    ..mechanisms have been proposed to explain the inhibitory activity of CTLA4: competition for B7-1 and B7-2 binding by CD28; sequestration of signaling molecules away from CD28 via endocytosis; delivery of a signal that antagonizes a CD28 ..
  68. pmc Studies in B7-deficient mice reveal a critical role for B7 costimulation in both induction and effector phases of experimental autoimmune encephalomyelitis
    T T Chang
    Immunology Research Division, Department of Pathology, Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Exp Med 190:733-40. 1999
    ..In this study, the role of B7-CD28 costimulation and the relative importance of B7 costimulators for the induction and effector phases of experimental ..
  69. ncbi The role of B7 costimulation in CD4/CD8 T cell homeostasis
    X Yu
    Experimental Immunology Branch, National Cancer Institute, and National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 164:3543-53. 2000
    ..B7-induced T cell expansion was dependent on both CD28 and TCR expression...
  70. ncbi A point mutation in CD28 distinguishes proliferative signals from survival signals
    K Okkenhaug
    Department of Immunology, University of Toronto, Ontario M5S 1A2, Canada
    Nat Immunol 2:325-32. 2001
    Upon interaction with its ligand, B7, CD28 becomes phosphorylated on tyrosines. One tyrosine in particular (Y170 in mouse CD28, Y173 in human CD28) has received much attention...
  71. ncbi Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection
    Edward M Bertram
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada
    J Immunol 168:3777-85. 2002
    In this report, we demonstrate that CD28(-/-) mice are severely impaired in the initial expansion of D(b)/NP366-374-specific CD8 T cells in response to influenza virus infection, whereas 4-1BB ligand (4-1BBL)(-/-) mice show no defect in ..
  72. pmc Impaired germinal centre formation and humoral immune response in the absence of CD28 and interleukin-4
    Rudolph Reiter
    Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany
    Immunology 106:222-8. 2002
    ..dependent one via the T cell receptor, the second one is a costimulatory signal which can be delivered by the CD28 molecule after binding to CD80 (B7.1) or CD86 (B7.2)...
  73. ncbi Constitutive expression of B7-1 on B cells uncovers autoimmunity toward the B cell compartment in the nonobese diabetic mouse
    Helene Bour-Jordan
    University of California, San Francisco Diabetes Center, Department of Medicine, CA 94143, USA
    J Immunol 179:1004-12. 2007
    ....
  74. pmc Identification of residues in the V domain of CD80 (B7-1) implicated in functional interactions with CD28 and CTLA4
    C A Fargeas
    Laboratoire d Immunologie, Institut de Recherches Cliniques de Montreal, Quebec, Canada
    J Exp Med 182:667-75. 1995
    ..CD80 can provide a critical costimulatory signal to T cells by interacting with the T cell surface molecule CD28. CD80 also binds to the CD28-related molecule CTLA4, which is expressed on activated T cells, Recently, additional ..
  75. ncbi Impaired negative selection in CD28-deficient mice
    P J Noel
    Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Illinois 60637, USA
    Cell Immunol 187:131-8. 1998
    ..In peripheral T cells, the CD28 receptor plays an important role in enhancing the survival and expansion of T cells activated by TCR engagement...
  76. ncbi Critical requirement for the membrane-proximal cytosolic tyrosine residue for CD28-mediated costimulation in vivo
    Y Harada
    Research Institute for Biological Sciences, Science University of Tokyo, Yamazaki, Noda, Chiba, Japan
    J Immunol 166:3797-803. 2001
    The YMNM motif that exists in the CD28 cytoplasmic domain is known as a binding site for phosphatidylinositol 3-kinase and Grb-2 and is considered to be important for CD28-mediated costimulation...
  77. ncbi Differential regulation of Th1 and Th2 functions of NKT cells by CD28 and CD40 costimulatory pathways
    Y Hayakawa
    Department of Pathogenic Biochemistry, Research Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
    J Immunol 166:6012-8. 2001
    ..We show here that NKT cells constitutively express CD28, and that blockade of CD28-CD80/CD86 interactions by anti-CD80 and anti-CD86 mAbs inhibits the alpha-GalCer-induced ..
  78. ncbi OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells
    P R Rogers
    Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
    Immunity 15:445-55. 2001
    ..We show that OX40 (CD134) is required with CD28 for the survival of CD4 T cells following antigen-driven expansion...
  79. ncbi A role for the B7-1/B7-2:CD28/CTLA-4 pathway during negative selection
    Janet E Buhlmann
    Department of Pathology, Immunology Research Division, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 170:5421-8. 2003
    ..Studies using CD28-deficient and CD28/CTLA-4-double-deficient mice have revealed that either CD28 or another as yet undefined ..
  80. ncbi Fine mapping, gene content, comparative sequencing, and expression analyses support Ctla4 and Nramp1 as candidates for Idd5.1 and Idd5.2 in the nonobese diabetic mouse
    Linda S Wicker
    Juvenile Diabetes Research Foundation Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK
    J Immunol 173:164-73. 2004
    ..only four genes, Ctla4, Icos, Als2cr19, and Nrp2 (neuropilin-2), thereby excluding a major candidate gene, Cd28. Genomic sequence comparison of the two functional candidate genes, Ctla4 and Icos, from the B6 (resistant at Idd5...
  81. ncbi B7-CD28 interaction promotes proliferation and survival but suppresses differentiation of CD4-CD8- T cells in the thymus
    Xincheng Zheng
    Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH 43210, USA
    J Immunol 173:2253-61. 2004
    ..Qualitatively similar, but quantitatively less striking effects were observed in mice with a targeted mutation of CD28, but not CTLA4...
  82. ncbi Cutting edge: CD28-mediated transcriptional and posttranscriptional regulation of IL-2 expression are controlled through different signaling pathways
    Mariano Sanchez-Lockhart
    David H Smith Center for Vaccine Biology and Immunology, Aab Institute, Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA
    J Immunol 173:7120-4. 2004
    Despite the clear functional importance of CD28 costimulation, the signaling pathways transduced through CD28 have remained controversial...
  83. doi Cutting edge: CD28 engagement releases antigen-activated invariant NKT cells from the inhibitory effects of PD-1
    Jianxiong Wang
    Department of Biochemistry and Molecular Biology, Julia McFarlane Diabetes Research Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    J Immunol 182:6644-7. 2009
    ..1 and costimulatory molecules on the surface of cognate Ag-presenting dendritic cells and that iNKT cells require a CD28 signal to secrete cytokines in the presence of a PD-1/PD ligand 1 interaction...
  84. ncbi Comparison of thymocyte development and cytokine production in CD7-deficient, CD28-deficient and CD7/CD28 double-deficient mice
    C S Heinly
    Division of Rheumatology, Allergy and Clinical Immunology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Int Immunol 13:157-66. 2001
    CD7 and CD28 are Ig superfamily molecules expressed on thymocytes and mature T cells that share common signaling 0mechanisms and are co-mitogens for T cell activation...
  85. pmc Topological requirements and signaling properties of T cell-activating, anti-CD28 antibody superagonists
    Fred Luhder
    Institute for Virology and Immunobiology, University of Wurzburg, Versbacher Str 7, D 97078 Wurzburg, Germany
    J Exp Med 197:955-66. 2003
    ..T cells requires both engagement of the T cell antigen receptor (TCR; signal 1) and costimulatory signaling by CD28 (signal 2)...
  86. ncbi A new role for CD28 in the survival of autoreactive T cells in the periphery after chronic exposure to autoantigen
    Jian Xin Gao
    Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA
    Int Immunol 16:1403-9. 2004
    ..The role of CD28 in the survival of autoreactive T cells in the periphery, however, has not been reported...
  87. ncbi A novel role for CD28 in thymic selection: elimination of CD28/B7 interactions increases positive selection
    Melanie S Vacchio
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, USA
    Eur J Immunol 35:418-27. 2005
    While the importance of the CD28/B7 costimulation pathway is well established for mature T cells, the role of CD28 in thymocyte selection is less well defined...
  88. pmc CTLA-4 on alloreactive CD4 T cells interacts with recipient CD80/86 to promote tolerance
    Josef Kurtz
    Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
    Blood 113:3475-84. 2009
    ..Animals lacking CD80 and CD86 failed to achieve chimerism. We detected no T cell-intrinsic requirement for CD28 for chimerism induction...
  89. ncbi Localization of growth arrest-specific genes on mouse chromosomes 1, 7, 8, 11, 13, and 16
    M P Colombo
    Division of Experimental Oncology D, Istituto Nazionali Tumori, Milano, Italy
    Mamm Genome 2:130-4. 1992
    ..The six genes are unlinked. Gas-1 maps to Chromosome (Chr) 13, Gas-2 to Chr 7, Gas-3 to Chr 11, Gas-4 to Chr 16, Gas-6 to Chr 8, and Gas-10 to Chr 1...
  90. ncbi In vivo blockade of CD28/CTLA4: B7/BB1 interaction with CTLA4-Ig reduces lethal murine graft-versus-host disease across the major histocompatibility complex barrier in mice
    B R Blazar
    Department of Pediatrics, University of Minnesota Hospital and Clinic, Minneapolis
    Blood 83:3815-25. 1994
    ..the in vivo infusion of recombinant, soluble CTLA4 fused with Ig heavy chains, as a surrogate ligand used to block CD28/CTLA4 T-cell costimulation, could prevent efficient T-cell activation and thereby reduce graft-versus-host disease (..
  91. ncbi Naive CD28-deficient T cells can initiate but not sustain an in vitro antigen-specific immune response
    P J Lucas
    Howard Hughes Medical Institute, Washington School of Medicine, St Louis, MO 63110, USA
    J Immunol 154:5757-68. 1995
    ..We have generated a CD28-deficient mouse that has been bred to a TCR transgenic (Tg) mouse to better study the function of CD28 during CD4+ ..
  92. ncbi Interleukin-12-activated natural killer cells recognize B7 costimulatory molecules on tumor cells and autologous dendritic cells
    A B Geldhof
    Laboratory of Cellular Immunology, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel VUB, Brussels
    Blood 91:196-206. 1998
    ..b>CD28 is functionally involved in the recognition of B7 on target cells since IL-2/IL-12-activated NK cells derived from ..
  93. ncbi Synergy between CD28 and CD9 costimulation for naive T-cell activation
    K Toyo-oka
    Biomedical Research Center, Osaka University Medical School, Japan
    Immunol Lett 58:19-23. 1997
    ..expressed on most mature naive T-cells and delivers a potent costimulatory signal that functions independently of CD28. Here, we investigated whether this CD9-mediated signal is different from the CD28-mediated signal in the mode of ..
  94. pmc Several different cell surface molecules control negative selection of medullary thymocytes
    H Kishimoto
    Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA
    J Exp Med 190:65-73. 1999
    ..In support of this idea, we show here that at least three cell surface molecules, namely CD28, CD5, and CD43, contribute to Fas-independent negative selection of the tolerance-susceptible population of heat-..
  95. ncbi Coordinate regulation of T cell activation by CD2 and CD28
    J M Green
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 164:3591-5. 2000
    ..However, the exact mechanism of costimulatory function is unknown. Mice lacking CD2 or CD28 show only mild deficits, demonstrating that neither protein is essential for T cell activation...
  96. ncbi The tyrosine kinase p56lck is essential in coxsackievirus B3-mediated heart disease
    P Liu
    Heart and Stroke Lewar Centre of Excellence in Cardiovascular Research, University of Toronto, University Health Network, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4
    Nat Med 6:429-34. 2000
    ..These data identify a previously unknown function of Src family kinases and indicate that p56lck is the essential host factor that controls the replication and pathogenicity of CVB3...
  97. ncbi Role of TNF receptor-associated factor 2 and p38 mitogen-activated protein kinase activation during 4-1BB-dependent immune response
    J L Cannons
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada Howard Hughes Medical Institute and Rockefeller University, New York, NY 10021, USA
    J Immunol 165:6193-204. 2000
    ..Previous results showed that 4-1BB-mediated T cell costimulation is CD28-independent and involves recruitment of TNFR-associated factor 2 (TRAF2) and activation of the stress-activated ..
  98. ncbi B7 requirements for primary and secondary protein- and polysaccharide-specific Ig isotype responses to Streptococcus pneumoniae
    Z Q Wu
    Departments of Pathology and Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Immunol 165:6840-8. 2000
    ..These studies demonstrate a critical, but variable, role for B7-dependent costimulation during an Ig response to an extracellular bacteria...
  99. ncbi CD40 signaling replaces CD4+ lymphocytes and its blocking prevents chronic rejection of heart transplants
    M P Fischbein
    Department of Microbiology, Immunology, and Molecular Genetics, Division of Cardiothoracic Surgery, University of California Los Angeles School of Medicine, Los Angeles, CA 90095, USA
    J Immunol 165:7316-22. 2000
    ..The CD40 signaling pathway works independently of B7-CD28 costimulation, as indicated by the development of severe chronic rejection in CD28 knockout recipients...
  100. pmc Identification of the CD4(+) T cell as a major pathogenic factor in ischemic acute renal failure
    M J Burne
    Division of Nephrology, Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota, USA
    J Clin Invest 108:1283-90. 2001
    ..In addition, adoptive transfers of CD4(+) T cells lacking either the costimulatory molecule CD28 or the ability to produce IFN-gamma were inadequate to restore injury phenotype...
  101. ncbi Homeostatic expansion occurs independently of costimulatory signals
    M Prlic
    Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
    J Immunol 167:5664-8. 2001
    ..that homeostatic expansion of CD4 and CD8 T cells occurs independently of costimulation signals mediated through CD28/B7, CD40L/CD40, or 4-1BB/4-1BBL interactions. Using DO11...

Research Grants11

  1. Crimson - i2b2 integration for high-throughput, scalable sample collection
    Lynn Bry; Fiscal Year: 2010
    ....
  2. T Cell Memory to Respiratory Viral Infections
    Shahram Salek Ardakani; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  3. IMMUNOTOXICOLOGY OF A HEAVY METAL
    Kenneth Pollard; Fiscal Year: 2004
    ..Analysis of the interaction between fibrillarin, mercury and cells of the lymphoid system may lead to insights into how an imunotoxin renders self-antigen immunogenic. ..
  4. Protective role of cross-reactive anti-enteric antibody
    Lynn Bry; Fiscal Year: 2005
    ....
  5. The Alternative NFkB Pathway in Survival and Function of Anti-Viral T Cells
    David Parker; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  6. BECTON DICKINSON FACS CALIBUR 4 COLOR WITH SORT UNIT
    Kenneth Pollard; Fiscal Year: 2001
    ..Flow cytometry will be used to select and sort cell populations prior to and after transplantation studies. ..
  7. XENOBIOTIC ACCELERATION OF AUTOIMMUNITY
    Kenneth Pollard; Fiscal Year: 2003
    ..abstract_text> ..
  8. Role of T cells in self-limited mucosal infections
    Lynn Bry; Fiscal Year: 2006
    ..This training provides a necessary step in the candidate's goal to become an independent researcher investigating questions in mucosal immunology and host-microbial cross-talk in intestinal environments. ..
  9. THE IMMUNOBIOLOGY OF MURINE ALLOGRAFT ACCEPTANCE
    Charles Cook; Fiscal Year: 2007
    ..In general, these studies will explore the immunobiology of murine allograft acceptance, and its relationship to allograft tolerance. ..
  10. MERCURY INDUCED AUTOIMMUNITY
    Kenneth Pollard; Fiscal Year: 2007
    ..Identification of the role that IFN-gamma plays in the development of induced murine systemic autoimmunity should prove applicable to murine models of idiopathic systemic autoimmunity and to human lupus. ..