Infections and The Stability of Transplantation Tolerance

Summary

Principal Investigator: Anita S Chong
Abstract: PROJECT SUMMARY (See Instructions): Project Overview Transplantation tolerance Is a dynamic immunological state that accommodates graft acceptance whilst maintaining undiminished immune responses to pathogens. We have recently demonstrated that the induction and preservation of transplantation tolerance can be differentially Impacted by pathogens that elicit distinct innate and adaptive immune signatures. These and other recent observations from our laboratories have led us to hypothesize that the quality of the tolerant state, either at the time of induction or during the maintenance phase, and the type of infection determine the long-term fate of the allograft. This is a new application requesting support for a highly integrated program project focused on understanding the cellular mechanisms in T cells that are necessary for a robust and persistent state of transplantation tolerance (i.e., tolerance that resists reversal by infections and permits long-term preservation of allograft function) (Project 1;Alegre) and understanding the short-term and long-term effects of infections on an already established state of transplantation tolerance (Project 2;Chong). Two Cores support the work of the two projects in the program. The Administrative Core (Core A, Chong) will oversee the administration of the program including the coordination of Progress Reports and co-ordinate meetings with the Internal and External Advisory Boards. The Animal and Microsurgery Core (Core B, Alegre) will be responsible for animal breeding and heart transplantations necessary for the two scientific projects. The Alegre and Chong laboratories have already been functioning as an integrated, cooperative program. Our investigations are revealing the complexity of the tolerant state as well as an unexpectedly divergent impact of infections on tolerance. There are few existing paradigms to guide these studies, thus the formal infrastructure of a Program Project will allow us to more seamlessly share personnel, data, resources, and to generate new hypotheses. Interactions with the internal and external advisory board members will allow new hypotheses and research designs to be vigorously vetted and improved upon. Successful completion of this program project will result in novel mechanistic and diagnostic insights into how transplantation tolerance can persist inspite of recurrent infections and achieve long-term allograft survival superior to current therapies.
Funding Period: 2012-07-17 - 2017-06-30
more information: NIH RePORT

Top Publications

  1. pmc Reversing endogenous alloreactive B cell GC responses with anti-CD154 or CTLA-4Ig
    J Chen
    Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL
    Am J Transplant 13:2280-92. 2013
  2. pmc Local inflammation exacerbates the severity of Staphylococcus aureus skin infection
    Christopher P Montgomery
    Department of Pediatrics, University of Chicago, Chicago, Illinois, USA
    PLoS ONE 8:e69508. 2013
  3. pmc Microbes and allogeneic transplantation
    Maria Luisa Alegre
    1 Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL 2 Section of Transplantation, Department of Surgery, University of Chicago, Chicago, IL 3 Address for Correspondence Maria Luisa Alegre, M D, Ph D, Section of Rheumatology, Department of Medicine, University of Chicago, 924 East 57th Street, JFK R312, Chicago, IL
    Transplantation 97:5-11. 2014
  4. pmc Lessons and limits of mouse models
    Anita S Chong
    Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, Illinois 60637
    Cold Spring Harb Perspect Med 3:a015495. 2013
  5. ncbi Impact of immunosuppression on recall immune responses to influenza vaccination in stable renal transplant recipients
    Michelle Cowan
    1 Department of Surgery, The University of Chicago, Chicago, IL 2 Department of Medicine, The University of Chicago, Chicago, IL 3 Department of Pathology, The University of Chicago, Chicago, IL 4 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 5 Atlanta Research and Education Foundation, Atlanta, GA 6 Address correspondence to Anita S Chong, Ph D, The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637
    Transplantation 97:846-53. 2014
  6. pmc Transplantation tolerance and its outcome during infections and inflammation
    Anita S Chong
    Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL, USA
    Immunol Rev 258:80-101. 2014

Research Grants

  1. STEM CELL GENE THERAPY FOR HEMOGLOBINOPATHIES
    George Stamatoyannopoulos; Fiscal Year: 2013
  2. Signaling in Inflammation, Stress, and Tumorigenesis
    GEORGE ROBERT STARK; Fiscal Year: 2013
  3. MOLECULAR BASIS OF CHOLESTEROL METABOLISM
    Joseph L Goldstein; Fiscal Year: 2013
  4. Martin Delaney Collaboratory to Eradicate HIV-1 Infection
    David M Margolis; Fiscal Year: 2013
  5. Herpesviral, Oncogenesis, Latency and Reactivation
    NANCY JOAN RAAB-TRAUB; Fiscal Year: 2013

Detail Information

Publications6

  1. pmc Reversing endogenous alloreactive B cell GC responses with anti-CD154 or CTLA-4Ig
    J Chen
    Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL
    Am J Transplant 13:2280-92. 2013
    ....
  2. pmc Local inflammation exacerbates the severity of Staphylococcus aureus skin infection
    Christopher P Montgomery
    Department of Pediatrics, University of Chicago, Chicago, Illinois, USA
    PLoS ONE 8:e69508. 2013
    ..Thus, the clinical severity of S. aureus skin infection is driven by the inflammatory response to the bacteria, rather than bacterial burden, in a T cell independent manner. ..
  3. pmc Microbes and allogeneic transplantation
    Maria Luisa Alegre
    1 Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL 2 Section of Transplantation, Department of Surgery, University of Chicago, Chicago, IL 3 Address for Correspondence Maria Luisa Alegre, M D, Ph D, Section of Rheumatology, Department of Medicine, University of Chicago, 924 East 57th Street, JFK R312, Chicago, IL
    Transplantation 97:5-11. 2014
    ..Here, we discuss known and hypothesized mechanisms for how infections or microbiota-derived signals may affect local or systemic alloimmunity and briefly review data on downstream effects of antibiotics and vaccinations. ..
  4. pmc Lessons and limits of mouse models
    Anita S Chong
    Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, Illinois 60637
    Cold Spring Harb Perspect Med 3:a015495. 2013
    ....
  5. ncbi Impact of immunosuppression on recall immune responses to influenza vaccination in stable renal transplant recipients
    Michelle Cowan
    1 Department of Surgery, The University of Chicago, Chicago, IL 2 Department of Medicine, The University of Chicago, Chicago, IL 3 Department of Pathology, The University of Chicago, Chicago, IL 4 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 5 Atlanta Research and Education Foundation, Atlanta, GA 6 Address correspondence to Anita S Chong, Ph D, The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637
    Transplantation 97:846-53. 2014
    ....
  6. pmc Transplantation tolerance and its outcome during infections and inflammation
    Anita S Chong
    Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL, USA
    Immunol Rev 258:80-101. 2014
    ..Understanding the mechanisms by which infections prevent and destabilize tolerance can lead to therapies that promote stable life-long tolerance in transplant recipients. ..

Research Grants30

  1. STEM CELL GENE THERAPY FOR HEMOGLOBINOPATHIES
    George Stamatoyannopoulos; Fiscal Year: 2013
    ..The focus of this Program Project, Gene Therapy, can provide a new paradigm for the treatment of these hemoglobinopathies as well as for other blood diseases. (End of Abstract) ..
  2. Signaling in Inflammation, Stress, and Tumorigenesis
    GEORGE ROBERT STARK; Fiscal Year: 2013
    ..abstract_text> ..
  3. MOLECULAR BASIS OF CHOLESTEROL METABOLISM
    Joseph L Goldstein; Fiscal Year: 2013
    ..Such an integrated interdisciplinary approach is possible only through continued support of this PPG. ..
  4. Martin Delaney Collaboratory to Eradicate HIV-1 Infection
    David M Margolis; Fiscal Year: 2013
    ..We are convinced that together we will catalyze advances that will ultimately lead to the eradication of HIV infection. ..
  5. Herpesviral, Oncogenesis, Latency and Reactivation
    NANCY JOAN RAAB-TRAUB; Fiscal Year: 2013
    ..abstract_text> ..