Immunological memory ensures that, once infected by a particular virus or bacteria, individuals are generally protected from a second encounter with that same pathogen. This ability of lymphocytes to “remember” is the basis for protection following vaccination. Little is known about the signaling pathways and molecular mechanisms that regulate the formation and maintenance of memory T cell numbers and functional capacity.
CD8+ T cells are crucial to the control of infection by pathogens that reside in the cytoplasm such as viruses, intracellular bacteria and protozoan parasites. CD8+ T cells recognize pathogen-derived peptides presented by MHC class I molecules, acting as sentinels in the detection of foreign cytoplasmic proteins. Upon encounter with antigen, naive CD8+ T cells proliferate and differentiate to effector T cells, which are armed to eliminate infected cells. Following antigen clearance, the majority of CD8+ effector cells die; however, a subset survive and differentiate further to long-lived memory T cells.
The goal of our research is to understand how CD8+ T cell immunological memory is generated and maintained by identifying the transcriptional and signaling events that regulate the survival and differentiation of T cells as they navigate the immune response and become long-lived memory T cells.
Rubinstein, M.P., Lind, N.A., Purton, J.F., Filippou, P., Best, J.A., McGhee, P.A., Surh, C.D., and Goldrath, A.W. (2008). IL-7 and IL-15 differentially regulate CD8+ T cell subsets during contraction of the immune response. Blood 112:3704-3712.
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 101:16885-91680.
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. She is also a Pew Scholar.