Antigen presentation to T cells in nonlymphoid tissue

描述（由申请方提供）：已经明确，次级淋巴器官中的抗原呈递对于抗原特异性适应性免疫应答的启动至关重要。这种应答的初级阶段由树突状细胞在MHC II背景下的抗原呈递组成，然后由CD4+ T细胞识别，CD4+ T细胞继而可以被激活。活化的效应CD4+ T细胞迁移回抗原沉积部位，在那里它们可以保留数周。该建议旨在确定抗原呈递在非淋巴组织中对CD4+ T细胞的作用。虽然我们预期组织中的炎性环境同等地启动效应T细胞的进入，但我们假设为了发生最大积累、隔离和持续活化，抗原特异性T细胞必须在抗原沉积的实际位点处的MHC II背景下识别同源抗原。我们的假设是，虽然树突状细胞活化淋巴结中的T细胞，但组织中的巨噬细胞负责抗原沉积部位的抗原呈递以及CD4+ T细胞的持续活化和保留。

DESCRIPTION (provided by applicant): It has been well established that antigen presentation in secondary lymphoid organs is essential for the initiation of an antigen specific adaptive immune response. The primary phase of this response consists of antigen presentation by dendritic cells in the context of MHC II where it is then recognized by CD4+ T cells which in turn can become activated. Activated effector CD4+ T cells migrate back into sites of antigen deposition where they can remain for weeks. This proposal seeks to determine the role of antigen presentation in nonlymphoid tissues with respect to its effect on CD4+ T cells. While we expect that the inflammatory milieu in the tissue initiates the entry of effector T cells equally, we hypothesize that in order for maximal accumulation, sequestration, and sustained activation to occur, antigen-specific T cells must recognize cognate antigen in the context of MHC II at the actual site of antigen deposition. Our hypothesis is that while dendritic cells activate T cells in the lymph nodes, macrophages in the tissue is responsible for antigen presentation at the site of antigen deposition and for the sustained activation and retention of CD4+ T cells.