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"IL-12 regulated checkpoints in the CD8+ T cell response to Toxoplasma gondii"

by
Suhagi Shah
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.
Associate Professor
Department of Medicine

Wednesday, August 20, 2014
1:00 P.M., MSB, Rosemary Gellene Room, B 515


Abstract

We have previously shown that IL-12 is necessary for the differentiation of KLRG1+ IFN--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--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- and IFN--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.


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