18. GOALS FOR FELLOWSHIP TRAINING AND CAREER The training goals for my fellowship are to become more knowledgeable in basic T cell immunology, to learn and apply current cellular based immunological methods, and to gain the confidence and knowledge to develop insightful and novel e3periments independently. My previous research experience involved using molecular techniques to observe gene rearrangements and protein/gene expression in B cells. The project proposed in my fellowship provides the opportunity to analyze T cells in a cellular based context and better understand which factor(s) are integral in the generation of memory T cells in vivo. At the conclusion of my fellowship, I hope to be able to mesh together my previous molecular immunology experience with the cellular based applications to independently assess various regulators of memory T cell development. 19. NAME AND DEGREE(S) Leo Lefrancois_ Ph.D. 20. POSITION/RANK Professor of Medicine 21. RESEARCH INTERESTS/AREAS T Cell Memory 22. DESCRIPTION (Do not exceed space provided) 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 CDS+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-7Rtx h_and IL-7R(_ = 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-lL7Rt_ 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-IL7Rct 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. PHS 416-1 (Rev. 12198) Form Page 2 BB CC Individual NRSA Application Table of Contents ========================================Section End===========================================
| Zammit, David J; Turner, Damian L; Klonowski, Kimberly D et al. (2006) Residual antigen presentation after influenza virus infection affects CD8 T cell activation and migration. Immunity 24:439-49 |
| Klonowski, Kimberly D; Marzo, Amanda L; Williams, Kristina J et al. (2006) CD8 T cell recall responses are regulated by the tissue tropism of the memory cell and pathogen. J Immunol 177:6738-46 |
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| Klonowski, Kimberly D; Williams, Kristina J; Marzo, Amanda L et al. (2004) Dynamics of blood-borne CD8 memory T cell migration in vivo. Immunity 20:551-62 |
| Marzo, Amanda L; Vezys, Vaiva; Klonowski, Kimberly D et al. (2004) Fully functional memory CD8 T cells in the absence of CD4 T cells. J Immunol 173:969-75 |
