ROLE OF COMMON GAMMA CHAIN CYTOKINES: MEMORY CD8 T CELLS

University Of Connecticut Sch Of Med/Dnt, Farmington CT

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Abstract

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.