Infections and The Stability of Transplantation Tolerance
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
- Reversing endogenous alloreactive B cell GC responses with anti-CD154 or CTLA-4IgJ Chen
Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL
Am J Transplant 13:2280-92. 2013....
- Local inflammation exacerbates the severity of Staphylococcus aureus skin infectionChristopher 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. ..
- Microbes and allogeneic transplantationMaria 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. ..
- Lessons and limits of mouse modelsAnita S Chong
Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, Illinois 60637
Cold Spring Harb Perspect Med 3:a015495. 2013....
- Impact of immunosuppression on recall immune responses to influenza vaccination in stable renal transplant recipientsMichelle 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....
- Transplantation tolerance and its outcome during infections and inflammationAnita 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. ..
- STEM CELL GENE THERAPY FOR HEMOGLOBINOPATHIESGeorge 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) ..
- Signaling in Inflammation, Stress, and TumorigenesisGEORGE ROBERT STARK; Fiscal Year: 2013..abstract_text> ..
- MOLECULAR BASIS OF CHOLESTEROL METABOLISMJoseph L Goldstein; Fiscal Year: 2013..Such an integrated interdisciplinary approach is possible only through continued support of this PPG. ..
- Martin Delaney Collaboratory to Eradicate HIV-1 InfectionDavid M Margolis; Fiscal Year: 2013..We are convinced that together we will catalyze advances that will ultimately lead to the eradication of HIV infection. ..
- Herpesviral, Oncogenesis, Latency and ReactivationNANCY JOAN RAAB-TRAUB; Fiscal Year: 2013..abstract_text> ..