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TNF receptor-associated factor 5 is required for optimal T cell expansion and survival in response to infection
Journal article   Peer reviewed

TNF receptor-associated factor 5 is required for optimal T cell expansion and survival in response to infection

Zachary J Kraus, Jodie S Haring and Gail A Bishop
The Journal of immunology (1950), Vol.181(11), pp.7800-7809
12/01/2008
DOI: 10.4049/jimmunol.181.11.7800
PMCID: PMC2636746
PMID: 19017969

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Abstract

Receptors belonging to the TNF-receptor (TNF-R) superfamily include important costimulatory molecules, many of which specifically affect T cell activation. Tumor necrosis factor 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 here that TRAF5 was required for optimal CD8 + T cell responses following infection with Listeria monocytogenes expressing ovalbumin (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 antigen presenting cells. Although their proliferative ability remained intact, CD8 + T cells from TRAF5 -/- mice were more sensitive to apoptosis and were unresponsive to the pro-survival 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 antigen-specific CD8 + T cells during infection.
TRAF Cell Activation T cell Apoptosis

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