{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:33:49Z","timestamp":1791214429246,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"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":[[2013,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inflammatory and anti-inflammatory cytokines play an important role in the generation of effector and memory CD8+ T cells. We used two different models, transgenic expression of truncated (dominant negative) form of TGF-\u03b2RII (dnTGF\u03b2RII) and Cre-mediated deletion of the floxed TGF-\u03b2RII to examine the role of TGF-\u03b2 signaling in the formation, function, and homeostatic proliferation of memory CD8+ T cells. Blocking TGF-\u03b2 signaling in effector CD8+ T cells using both of these models demonstrated a role for TGF-\u03b2 in regulating the number of short-lived effector cells but did not alter memory CD8+ T cell formation and their function upon Listeria monocytogenes infection in mice. Interestingly, however, a massive lymphoproliferative disorder and cellular transformation were observed in Ag-experienced and homeostatically generated memory CD8+ T cells only in cells that express the dnTGF\u03b2RII and not in cells with a complete deletion of TGF-\u03b2RII. Furthermore, the development of transformed memory CD8+ T cells expressing dnTGF\u03b2RII was IL-7\u2013 and IL-15\u2013independent, and MHC class I was not required for their proliferation. We show that transgenic expression of the dnTGF\u03b2RII, rather than the absence of TGF-\u03b2RII\u2013mediated signaling, is responsible for dysregulated expansion of memory CD8+ T cells. This study uncovers a previously unrecognized dominant function of the dnTGF\u03b2RII in CD8+ T cell proliferation and cellular transformation, which is caused by a mechanism that is different from the absence of TGF-\u03b2 signaling. These results should be considered during both basic and translational studies where there is a desire to block TGF-\u03b2 signaling in CD8+ T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1300397","type":"journal-article","created":{"date-parts":[[2013,5,18]],"date-time":"2013-05-18T04:37:56Z","timestamp":1368851876000},"page":"6340-6350","source":"Crossref","is-referenced-by-count":46,"title":["Truncated Form of TGF-\u03b2RII, But Not Its Absence, Induces Memory CD8+ T Cell Expansion and Lymphoproliferative Disorder in Mice"],"prefix":"10.1093","volume":"190","author":[{"given":"Harumichi","family":"Ishigame","sequence":"first","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munir M","family":"Mosaheb","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shomyseh","family":"Sanjabi","sequence":"additional","affiliation":[{"name":"Gladstone Institutes , San Francisco, CA 94158"},{"name":"Department of Microbiology and Immunology, University of California , San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Flavell","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Howard Hughes Medical Institute , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,6,15]]},"reference":[{"key":"2025032407044723900_r1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1600-065X.2010.00926.x","article-title":"Generation of effector CD8+ T cells and their conversion to memory T cells","volume":"236","author":"Cui","year":"2010","journal-title":"Immunol. 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