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The Journal of Immunology, 2008, 181, 7131 -7137
Copyright © 2008 by The American Association of Immunologists, Inc.
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TNF-{alpha} Is a Positive Regulatory Factor for Human V{gamma}2V{delta}2 T Cells1

Haishan Li, Kun Luo and C. David Pauza2

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201

V{gamma}2V{delta}2 T cells in human peripheral blood recognize phosphoantigen and play important roles in host defense and immunoregulation. The TCR is required for V{gamma}2V{delta}2 T cell responses to phosphoantigen, but less is known about soluble or cell-associated costimulatory molecules. In this study, we show that human V{gamma}2V{delta}2 T cell responses to phosphoantigen, including activation, proliferation, cytokine production, and tumor cell cytotoxicity, require TNF-{alpha} binding to its receptor, with a preference for TNFR2. Because stimulated V{gamma}2V{delta}2 cells also produce TNF-{alpha}, this may be a positive control mechanism to sustain the response. Impaired proliferation in the presence of TNF-{alpha} or TNFR blocking agents was partially rescued by a TLR2 agonist, Pam3Cys. Our studies demonstrate that TNF-{alpha} plays a critical role in regulating human V{gamma}2V{delta}2 T cell immune responses.

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 Public Health Service Grant AI077059 (to C.D.P.).

2 Address correspondence and reprint requests to Dr. C. David Pauza, 725 West Lombard Street, Room N546, Baltimore, MD 21201. E-mail address: cdpauza{at}ihv.umaryland.edu

3 Abbreviations used in this paper: DC, dendritic cell; IPP, isopentyl pyrophosphate.






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