{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T22:52:51Z","timestamp":1772923971615,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2008,12,1]],"date-time":"2008-12-01T00:00:00Z","timestamp":1228089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2212\/\u2212 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.<\/jats:p>","DOI":"10.4049\/jimmunol.181.11.7800","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:09:53Z","timestamp":1397848193000},"page":"7800-7809","source":"Crossref","is-referenced-by-count":32,"title":["TNF Receptor-Associated Factor 5 Is Required for Optimal T Cell Expansion and Survival in Response to Infection"],"prefix":"10.1093","volume":"181","author":[{"given":"Zachary J","family":"Kraus","sequence":"first","affiliation":[{"name":"Graduate Program in Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jodie S","family":"Haring","sequence":"additional","affiliation":[{"name":"Department of Microbiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail A","family":"Bishop","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology"},{"name":"Department of Microbiology"},{"name":"Department of Internal Medicine, University of Iowa"},{"name":"Iowa City Veterans\u2019 Affairs Medical Center , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,12,1]]},"reference":[{"key":"2026012807132222600_R1","first-page":"5565","article-title":"Role of CD28-B7 interactions in generation and maintenance of CD8 T cell memory","volume-title":"J. Immunol.","year":"2001"},{"key":"2026012807132222600_R2","first-page":"456","article-title":"The generation of memory antigen-specific cytotoxic T cell responses by CD28\/CD80 interactions in the absence of antigen","volume-title":"Eur. J. Immunol.","year":"1997"},{"key":"2026012807132222600_R3","first-page":"433","article-title":"CD27 is required for generation and long-term maintenance of T cell immunity","volume-title":"Nat. Immunol.","year":"2000"},{"key":"2026012807132222600_R4","first-page":"445","article-title":"OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells","volume-title":"Immunity","year":"2001"},{"key":"2026012807132222600_R5","first-page":"265","article-title":"Costimulation of T cells by OX40, 4-1BB, and CD27","volume-title":"Cytokine Growth Factor Rev.","year":"2003"},{"key":"2026012807132222600_R6","first-page":"1665","article-title":"During viral infection of the respiratory tract, CD27, 4-1BB, and OX40 collectively determine formation of CD8+ memory T cells and their capacity for secondary expansion","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012807132222600_R7","first-page":"491","article-title":"Control of lymphocyte function through CD27-CD70 interactions","volume-title":"Semin. 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