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The Journal of Immunology, 2007, 179, 2115 -2125
Copyright © 2007 by The American Association of Immunologists, Inc.
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Role of Direct Effects of IFN-{gamma} on T Cells in the Regulation of CD8 T Cell Homeostasis1

Kavita Tewari, Yumi Nakayama and M. Suresh2

Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706

It is well recognized that IFN-{gamma} plays a critical role in the control of CD8 T cell expansion and contraction during immune responses to several intracellular pathogens. However, our understanding of the mechanisms underlying the regulation of T cell fate by IFN-{gamma} is sorely incomplete. Specifically, it is unclear whether regulation of CD8 T cell homeostasis occurs by a T cell intrinsic IFN-{gamma} pathway. In this study, we have determined the role of the direct effects of IFN-{gamma} on T cells in regulating the expansion, contraction, and memory phases of the polyclonal CD8 T cell response to an acute viral infection. Using two complementary approaches we demonstrate that the direct effects of IFN-{gamma} suppress IL-7R expression on Ag-specific effector CD8 T cells, but clonal expansion or deletion of activated CD8 T cells in vivo can occur in the apparent absence of IFN-{gamma}R signaling in T cells. These findings have clarified fundamental features of control of T cell homeostasis by IFN-{gamma} in the context of CD8 T cell memory and protective immunity.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by Grant AI059804 from the Public Health Service, National Institutes of Health (to M.S.).

2 Address correspondence and reprint requests to Dr. M. Suresh, Department of Pathobiological Sciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706. E-mail address: sureshm{at}svm.vetmed.wisc.edu

3 Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; DN, dominant negative; PI, postinfection; CD62L, CD62 ligand; MFI, mean fluorescence intensity; ROS, reactive oxygen species.




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