权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

CD4 Memory T Cells and Allograft Rejection

CD4 记忆 T 细胞和同种异体移植排斥

基本信息

批准号：
8078592
负责人：
Anna Valujskikh
金额：
$ 15.7万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8078592
关键词：
Affect Alloantigen Allografting Animals Antigens B-Lymphocytes Blood Circulation CD4 Positive T Lymphocytes Cell physiology Cells Characteristics Data Development Effector Cell Exposure to Generations Goals Graft Rejection Human Immune response Immunobiology Immunosuppressive Agents Immunotherapy Infection Integrins Isoantibodies L-Selectin Lead Liver Location Longevity Lung Lymphocyte Homing Receptors Lymphoid Lymphoid Tissue Mediating Memory Modeling Mus Organ Organ Transplantation Outcome Pathway interactions Patients Pattern Peripheral Pharmaceutical Preparations Phenotype Population Predisposition Property Resistance Risk Role SELL gene Surface T memory cell T-Lymphocyte T-Lymphocyte Subsets Testing Tissues Translating Transplantation allograft rejection base cell motility combinatorial heart allograft improved in vivo insight lymph nodes memory CD4 T lymphocyte pathogen population based research study trafficking

项目摘要

Memory T cells specific for donor antigens present a unique challenge in transplantation. While memory T cells augment host protection upon re-infection, donor-reactive memory T cells lead to robust immune responses to a transplanted organ translating into increased risk of poor allograft outcome in humans. Furthermore, memory T cells appear to be resistant to the effects of currently used graft-prolonging therapies including immunosuppressive drugs, depletional strategies and conventional costimulatory blockade. The existence of two populations of memory CD4 T cells has been proposed based on distinct migratory properties. While central memory CD4 T cells reside in secondary lymphoid organs, effector memory CD4 T cells preferentially circulate through non-lymphoid peripheral tissues and perform pathogen surveillance. The functions of these memory C04 T cells subsets, their contribution to allograft rejection and susceptibility to the currently used immunotherapies remain unknown and need to be tested. The goal of the proposed studies is to determine how the anatomical location of lymphoid and peripheral alloreactive memory CD4T cells affects their activation, function and susceptibility to lymphoid sequestration and to costimulatory blockade. We hypothesize that lymphoid but not peripheral memory CD4T cells contribute to cardiac allograft rejection by providing help for the induction of donor-reactive CDST cells and alloantibody while peripheral memory CD4T cells migrate into the graft and express functions mediating tissue damage. We further hypothesize that costimulatory ICOS/B7RP-1 interactions are required for helper functions ofmemory CD4 T cells and for the migration of both memoryand newly generated effector T cells into the graft. To test this hypothesis, we propose to comparethe migratory properties and functions of lymphoid versus peripheral memory CD4 T cells, to test the effect of lymphoid sequestration on the function of lymphoidversus peripheral alloreactive memory CD4 T cells, and to determine the role of costimulation through ICOS/B7RP- 1 in the re-activation, trafficking and functions of lymphoid and peripheral memory CD4T cells. The results of the proposed experiments will provide mechanistic insights into the immunobiology of alloreactive memory CD4 T cells in allograft rejection. This information should contribute to the development of combinatorial therapies to improve allograft function and survival in sensitized patients.

对供体抗原特异的记忆T细胞在移植中提出了一个独特的挑战。而记忆T