Homeostatic Proliferation and Memory CD8 T Cells

描述（由申请人提供）：记忆性CD8+ T细胞对先前遇到的抗原提供必要的特异性免疫，这种细胞的形成是疫苗接种的基本目标。我们的数据显示，免疫前的CD8 T细胞群包含具有记忆样特性的细胞，我们称之为“稳态记忆”（HM）细胞。在这个提议中，我们将测试这群T细胞如何促进初级免疫反应。基于之前的数据，我们将实现两个目标。1) HM池如何在免疫反应早期对病原体作出反应，以及这些细胞如何影响免疫反应期间可能出现的病原体生长或免疫病理。我们还将扩展数据，表明HM细胞在对抗原的反应上与“na¿ve”细胞有质的不同。2)该目的扩展了初步数据，表明细胞因子IL-4在控制CD8 T细胞反应中起着意想不到的作用。我们将评估IL-4在控制记忆性CD8 T细胞维持中的功能，并基于我们的初步数据，通过确定IL-4介导其作用的阶段，显示IL-4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.