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,
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* Graduate Program in Immunology,
Department of Microbiology,
Department of Internal Medicine, University of Iowa, and
Iowa City Veterans’ Affairs Medical Center, Iowa City, IA 52242
Receptors belonging to the TNF-receptor (TNF-R) superfamily include important costimulatory molecules, many of which specifically affect T cell activation. TNF receptor-associated factors (TRAFs) are recruited to many TNF-R superfamily members and are important modulators of the proximal signaling events that occur at the time of receptor engagement and activation. TRAF5 has been shown to be a positive regulator of a number of these receptors that are involved in T cell costimulation. However, the potential importance of TRAF5 in cellular immune responses to infection or in T cell expansion and memory have not been studied. We report in this study that TRAF5 was required for optimal CD8+ T cell responses following infection with Listeria monocytogenes expressing OVA (LM-OVA). TRAF5 was necessary for optimal T cell expansion following primary infection with LM-OVA, and its absence resulted in fewer memory CD8+ T cells following LM-OVA infection, together with higher bacterial loads in the liver. The effect of TRAF5 on CD8+ T cell expansion was T cell intrinsic and not due to effects of TRAF5 deficiency on APCs. Although their proliferative ability remained intact, CD8+ T cells from TRAF5–/– mice were more sensitive to apoptosis and were unresponsive to the prosurvival effects of the TNF-R superfamily costimulator CD27. Collectively, these studies identify TRAF5 as an important positive signaling element that enhances T cell expansion and pathogen containment by providing a survival advantage to responding Ag-specific CD8+ T cells during infection.
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 is supported by a predoctoral fellowship awarded by the American Heart Association 0715658Z (to Z.J.K.) and by grants from the National Institute of Allergy and Infectious Disease, the National Cancer Institute, and the Veteran’s Administration (to G.A.B.).
2 Current address: North Dakota State University, Fargo, ND 58105.
3 Address correspondence and reprint requests to Dr. Gail A. Bishop, 2193, Medical Education and Research Facility, Department of Microbiology, University of Iowa, Iowa City, IA 52242. E-mail address: gail-bishop{at}uiowa.edu
4 Abbreviations used in this paper: TNF-R, TNF-receptor; TRAF, TNF receptor-associated factor; LM-OVA, Listeria monocytogenes expressing OVA; p.i., postinfection; DC, dendritic cell; ICS, intracellular cytokine staining; BMDC, bone marrow derived DC; WT, wild type; GITR, glucocorticoid-induced TNFR.
5 The online version of this article contains supplementary material.
This article has been cited by other articles:
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  T. J. Vanden Bush, C. M. Buchta, J. Claudio, and G. A. Bishop Cutting Edge: Importance of IL-6 and Cooperation between Innate and Adaptive Immune Receptors in Cellular Vaccination with B Lymphocytes J. Immunol., October 15, 2009; 183(8): 4833 - 4837. [Abstract] [Full Text] [PDF]
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 Z. J. Kraus, H. Nakano, and G. A. Bishop TRAF5 is a critical mediator of in vitro signals and in vivo functions of LMP1, the viral oncogenic mimic of CD40 PNAS, October 6, 2009; 106(40): 17140 - 17145. [Abstract] [Full Text] [PDF]
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