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Interdisciplinary Biomedical Sciences Program
MPH 2005, University of Medicine and Dentistry of New Jersey, Newark, NJ
B.S. 2003, University of the Sciences in Philadelphia, Philadelphia, PA
Thesis Advisor: George Yap, Ph.D.
Department of Medicine
Wednesday, August 20, 2014
1:00 P.M., MSB, Rosemary Gellene Room, B 515
We have previously shown that IL-12 is necessary for the differentiation of KLRG1+ IFN-ã-producing CD8+ T effector cells during the immune response to Toxoplasma gondii. However, which key events during the activation, differentiation and mobilization of CD8+ T effector cells are critically regulated by IL-12 have not been identified. By tracking the dynamics of endogenous and adoptively transferred T. gondii-reactive CD8+ T cells, we were able to identify two key IL-12 dependent checkpoints. First, IL-12 is critical for the early diversification of CD8+ T cells into KLRG1+ IFN-ã-producing CD8+ T effector cells, which occurs even prior to their initial proliferation. Acquisition of KLGR1 expression by CD8+ T effector cells was accompanied by an attenuation of CXCR3 expression and this down regulation was IL-12-dependent. Unexpectedly, this effect of IL-12 occurs in a non-cell autonomous fashion, through the induction of IFN-ã and IFN-ã-induced chemokines. Our study shows that IL-12 implements the early diversification of CD8+ T cells by both promoting and attenuating expression of key CD8+ T lymphocyte proteins required for their effector function and mobilization.