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Mediators of Inflammation
Volume 2013 (2013), Article ID 359674, 10 pages
Research Article

STAT3 Regulates Proliferation and Survival of CD8+ T Cells: Enhances Effector Responses to HSV-1 Infection, and Inhibits IL-10+ Regulatory CD8+ T Cells in Autoimmune Uveitis

1Molecular Immunology Section, National Eye Institute, National Institutes of Allergy and Viral Diseases, National Institutes of Health, Building 10, Room 10N109A, 10 Center Drive, Bethesda, MD 20892-1857, USA
2Cellular Biology and Viral Immunology Section, National Institutes of Allergy and Viral Diseases, National Institutes of Health, Building 33, Room 2E13, 33 North Drive, Bethesda, MD, USA

Received 22 April 2013; Accepted 19 August 2013

Academic Editor: Hidde Bult

Copyright © 2013 Cheng-Rong Yu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


STAT3 regulates CD4+ T cell survival and differentiation. However, its effects on CD8+ T cells are not well understood. Here, we show that in comparison to WT CD8+ T cells, STAT3-deficient CD8+ T cells exhibit a preactivated memory-like phenotype, produce more IL-2, proliferate faster, and are more sensitive to activation-induced cell death (AICD). The enhanced proliferation and sensitivity to AICD correlated with downregulation of class-O forkhead transcription factors (FoxO1, FoxO3A), , , Bcl-2, OX-40, and upregulation of FasL, Bax, and Bad. We examined whether STAT3-deficient CD8+ T cells can mount effective response during herpes simplex virus (HSV-1) infection and experimental autoimmune uveitis (EAU). Compared to WT mice, HSV-1-infected STAT3-deficient mice (STAT3KO) produced less IFN- and virus-specific KLRG-1+ CD8+ T cells. STAT3KO mice are also resistant to EAU and produced less IL-17-producing Tc17 cells. Resistance of STAT3KO to EAU correlated with marked expansion of IL-10-producing regulatory CD8+ T cells (CD8-Treg) implicated in recovery from autoimmune encephalomyelitis. Thus, increases of IL-6-induced STAT3 activation observed during inflammation may inhibit expansion of CD8-Tregs, thereby impeding recovery from uveitis. These results suggest that STAT3 is a potential therapeutic target for upregulating CD8+ T cell-mediated responses to viruses and suggest the successful therapeutic targeting of STAT3 as treatment for uveitis, derived, in part, from promoting CD8-Treg expansion.