Regulation of T Cells by the Cytokines IL-7 and IL-15

University Of Connecticut Sch Of Med/Dnt, Farmington CT

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Abstract

DESCRIPTION (provided by the applicant): Memory T cells are long-lived T cells which have previously encountered antigen and are poised for rapid response upon a secondary challenge. To date, the factor(s) involved in generating and maintaining the CD8 memory T cell pool remains an enigma. IL-7 is a well documented cytokine important for survival of CD8+T cells. Further, IL-15, a related cytokine, is also believed to be partially responsible for memory T cell development. The objective of this proposal is to evaluate the roles the two cytokines on memory T cell development and survival. To test whether IL-7 receptor (IL-7R) expression correlates with the generation of memory T cells, TCR transgenic IL-7R-alpha[hi] and IL-7R-alpha[lo] expressing activated T cells will be transferred into normal mice. Donor cell attrition and IL-7R expression will be monitored over time. Blocking experiments using an anti-IL7R-alpha mAb will pinpoint the stage at which IL-7 is essential for memory T cell generation. To look at the effects of both IL-7 and IL-15 on memory T cell development, memory T cells will be transferred into IL-15-/- mice followed by anti-IL-7R-alpha treatment. Together, these experiments will address the basic requirements for memory T cell development and may result in numerous clinical applications including augmenting vaccine efficacy.