{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:27:49Z","timestamp":1791221269639,"version":"4.1.0"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2007,8,17]],"date-time":"2007-08-17T00:00:00Z","timestamp":1187308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Public Health Service","award":["AI48785"],"award-info":[{"award-number":["AI48785"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>It is known that TNF-\u03b1 (TNF) exerts distinct tissue-protective or -destructive effects in the pathogenesis of T cell-dependent immunopathology, depending on the context and amount of cytokine produced. To better understand the cellular mechanisms underlying the regulation of T cells by TNF, we have analyzed the role of TNF in regulating various facets of the antigen-specific CD8 T cell response to lymphocytic choriomeningitis virus (LCMV) in mice. We show that expansion and differentiation of virus-specific effector CD8 T cells and LCMV clearance are not dependent on TNF. Instead, we demonstrate that TNF limits the duration of the effector phase of the CD8 T cell response by regulating apoptosis and not proliferation of effector cells in vivo. We further show that attenuation of effector cell apoptosis induced by TNF deficiency led to a substantial increase in the number of virus-specific memory CD8 T cells without affecting their function. The enhancement in the number of memory CD8 T cells in TNF-deficient (TNF\u2212\/\u2212) mice was not associated with up-regulation of IL-7R\u03b1 or Bcl-2 in effector cells, which indicated that TNF might limit differentiation of memory cells from IL-7Rlo effector cells. Collectively, these data are strongly suggestive of a role for TNF in down-regulating CD8 T cell responses and the establishment of CD8 T cell memory during an acute viral infection. These findings further our understanding of the regulation of CD8 T cell homeostasis and have implications in vaccine development and clinical use of anti-TNF therapies to treat T cell-dependent, inflammatory disorders.<\/jats:p>","DOI":"10.1189\/jlb.0407240","type":"journal-article","created":{"date-parts":[[2007,8,18]],"date-time":"2007-08-18T01:10:20Z","timestamp":1187399420000},"page":"1201-1211","source":"Crossref","is-referenced-by-count":26,"title":["A role for TNF in limiting the duration of CTL effector phase and magnitude of CD8 T cell memory"],"prefix":"10.1093","volume":"82","author":[{"given":"Anju","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin-Madison , Madison, Wisconsin , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Suresh","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin-Madison , Madison, Wisconsin , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,8,17]]},"reference":[{"key":"2023033006495553500_","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev.iy.10.040192.002211","article-title":"The pathophysiology of tumor necrosis factors","volume":"10","author":"Vassalli","year":"1992","journal-title":"Annu. 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