ROLE OF COMMON GAMMA CHAIN CYTOKINES: MEMORY CD8 T CELLS

负责产生和维持记忆T细胞群体的机制尚不清楚。推测特定的细胞因子可能促进CD8记忆T细胞的分化和存活。这项建议的目的是确定使用共同伽马链(Gammac)受体亚单位的细胞因子是否是产生或维持记忆CD8+T细胞所必需的。IL-2、IL-7和IL-15是细胞因子，它们通过含有伽马酸的受体发出信号，已被证明可以提高T细胞的存活率。因此，将检查体内对IL-2、IL-7和IL-15对CD8T细胞激活和记忆产生的要求。不能产生IL-2(OT-1/IL-2-/-)的OT-I T细胞(转基因TCR，在MHC I类背景下识别卵白蛋白多肽)将被过继转移到正常小鼠，并检测其向记忆性T细胞的扩增和分化能力。更重要的是。也会产生不能对IL-7或IL-15反应的OT-I T细胞(OT-I/IL-7Rpha-/-、OT-I/IL-15Rpha-)。这些OT-I T细胞将用于过继转移系统，其扩增和分化为记忆性T细胞的能力也将被确定。这些研究将有助于确定产生记忆T细胞的要求，从而促进疫苗的开发。

The mechanism that is responsible for generating and maintaining memory T cell populations is not known. It is hypothesized that specific cytokines may facilitate the differentiation and survival of CD8 memory T cells. The objective of this proposal is to determine whether the cytokines that use the common gamma chain (gammac) receptor subunit are required for generating or maintaining memory CD8+ T cells. IL-2, IL-7, and IL-15 are cytokines that signal through receptors that contain the gammac and have been shown to increase survival of T cells. Therefore, the in vivo requirements for IL-2, IL-7, and IL-15 for CD8 T cell activation and memory generation will be examined. OT-I T cells (transgenic for a TCR that recognizes an ovalbumin peptide in the context of MHC class I) which cannot produce IL-2 (OT-1/IL-2-/-) will be adoptively transferred into normal mice and their ability to expand and differentiate into memory T cells will be measured. Furthermore. OT-I T cells that cannot respond to IL-7 or IL-15 will also be produced (OT-I/IL-7Ralpha-/-, OT-I/IL-15Ralpha--). These OT-I T cells will be used in the adoptive transfer system and their ability to expand and differentiate into memory T cells will also be determined. These studies will help define the requirements for the generation of memory T cells and thus would facilitate vaccine development.