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Infections and The Stability of Transplantation Tolerance

感染和移植耐受的稳定性

基本信息

批准号：
8512659
负责人：
Anita S Chong
金额：
$ 107.15万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-17 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8512659
关键词：
Acute Address Allografting Animals Apoptosis Bacterial Infections Biological Preservation Cells Clinic Clinical Clonal Deletion Clonal Expansion Data Diagnosis Diagnostic Exhibits Goals Heart Transplantation Human Human Resources Immune Immune Tolerance Immune response Immunosuppression Immunosuppressive Agents Infection Infectious Agent Inflammatory Instruction Interferons Interleukin-6 Investigation Laboratories Life Listeria Listeriosis Long-Term Effects Maintenance Memory Microsurgery Monitor Mus Natural Immunity Pattern recognition receptor Pharmaceutical Preparations Phase Prevention Progress Reports Recurrence Regimen Regulation Request for Applications Research Research Design Research Infrastructure Residual state Resistance Resources Rodent Model Signal Transduction Stimulus T cell anergy T-Lymphocyte TNFSF5 gene Testing Therapeutic Time Transplantation Transplantation Immunology Transplantation Tolerance Virus Diseases Work adaptive immunity anergy animal breeding arm base clinically relevant cytokine exhaustion heart allograft improved insight meetings member novel pathogen prevent programs response success transcription factor

项目摘要

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.

项目总结（见说明）：项目概述