Regulation of naïve and memory T cell populations: T cells act as antigen-specific sentinels--standing guard, waiting to protect the body in the event of an attack by a pathogen. The peripheral T lymphocyte pool is homeostatically regulated to ensure optimal preparedness. Cell input, proliferation and death are integrated to insure that T cell numbers are maintained at remarkably stable levels throughout adulthood. The subset composition and number of cells within the immune system is very similar for individuals of the same species at the same age suggesting a “hard-wired” mechanism for regulating cell numbers. While many of the cellular and molecular interactions that underlie an active immune response are well characterized, little is understood about the factors that influence homeostasis of T cells in the time before or intervening antigen encounters. The molecular interactions controlling T cell survival, life span, and compartment size are the focus of our research. Initially, we are focusing on the role of T cell-receptor and IL-7-receptor, two molecules known to be essential for naïve T cells to persist for prolonged periods. We are also studying the differential survival requirements of naïve (antigen-inexperienced) and memory (antigen-experienced) T cells and have identified genes potentially important in the function and survival of memory T cells. Memory lymphocytes sustain the protective immunity obtained following antigen-encounter (infection or vaccination) and are long-lived and self-renewing. Relatively little is known about the molecular interactions that allow the maintenance of this important population. By expanding our understanding of how lymphocyte populations
are regulated, it will be possible to gain insight into how normal
survival signals are co-opted and how homeostatic set points
are overcome by cancer
cells. Furthermore, we hope to identify the key mediators of
memory T cell longevity to allow better vaccine design. Michael A. Cannarile, Nicholas A. Lind, Richard Rivera, Alison D. Sheridan, Kristin A. Camfield, Bei Bei Wu, Kitty P. Cheung, Zhaoqing Ding and Ananda W. Goldrath. (2006). A novel role for Id2 in the regulation of CD8+ T cell immunity. Nature Immunology. 7:1317-1325. Goldrath A. W., C. J. Luckey, R. Park, C. Benoist, D. Mathis. (2004). The molecular program induced in T cells undergoing homeostatic proliferation. PNAS 101:16885-90. Goldrath A.W., P.V. Sivakumar, M. Glaccum, M.K. Kennedy, M. J. Bevan, C. Benoist, D. Mathis, E.A. Butz. (2002). Cytokine requirements for acute and basal homeostatic proliferation of naive and memory CD8+ T cells. Journal of Experimental Medicine 195:49-52. Goldrath, A.W. and M.J. Bevan. (1999). Low-affinity ligands for the TCR drive proliferation of CD8+ T cells in lymphopenic hosts. Immunity 11: 183-190. Goldrath, A.W. and M.J. Bevan. (1999). Generating and maintaining a diverse T cell repertoire. Nature 402: 217-328. Goldrath, A.W., K. Hogquist, and M.J. Bevan. (1997). CD8 lineage commitment in the absence of CD8. Immunity 6:633-642. Ananda Goldrath received her Ph.D. from the University of Washington. She was a postdoc at the Joslin Diabetes Center at Harvard Medical School where she was the Juvenile Diabetes Research Foundation-Irvington Fellow. |
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