Homeostatic Proliferation and Memory CD8 T Cells

描述(由申请人提供)：记忆性CD8 T细胞提供对先前遇到的抗原的基本特异性免疫，而形成这种细胞是疫苗接种的基本目标。我们的数据显示，CD8T细胞的免疫前群体包含具有记忆样特性的细胞，我们称之为“内稳态记忆”(HM)细胞。在这项建议中，我们将测试这群T细胞如何对初级免疫反应做出贡献。在之前数据的基础上，我们将实现两个目标。1)HM池在免疫反应早期如何对病原体做出反应，以及这些细胞可能如何影响在免疫反应期间可能出现的病原体生长或免疫病理学。我们还将扩展数据，表明HM细胞在对抗原的反应方面与“NA”细胞有质的不同。2)这一目的扩大了初步数据，表明细胞因子IL-4在控制CD8 T细胞反应中发挥了意想不到的作用。我们将评估IL-4在控制记忆CD8 T细胞维持中的功能，并以我们的初步数据为基础，通过确定IL-4介导其作用的阶段来支持CD8对病原体的反应。

DESCRIPTION (provided by applicant): Memory CD8+ T cells provide essential specific immunity against previously encountered antigens, and formation of such cells is a fundamental goal of vaccination. Our data show that the pre-immune population of CD8 T cells contains cells with memory-like properties, which we call "Homeostatic memory" (HM) cells. In this proposal we will test how this population of T cells contributes to primary immune responses. Building on our previous data, we will conduct two aims. 1) how the HM pool responds to pathogens early during an immune response, and how these cells may affect pathogen growth or immunopathology that can arise during immune responses. We will also extend data suggesting HM cells differ qualitatively from "na¿ve" cells in their response to antigen. 2) This aim extends preliminary data suggesting the cytokine IL-4 plays an unexpected role in controlling CD8 T cell responses. We will assess the function of IL- 4 in controlling memory CD8 T cell maintenance, and build on our preliminary data showing that IL-4 supports the CD8 response to pathogens, by determining the stage at which IL-4 mediates its effects.