{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:12:58Z","timestamp":1789711978689,"version":"4.0.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2007,10,1]],"date-time":"2007-10-01T00:00:00Z","timestamp":1191196800000},"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":[[2007,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>T cell depletion is a widely used approach in clinical transplantation. However, not all T cells are equally sensitive to depletion therapies and a significant fraction of T cells persists even after aggressive treatment. The functional attributes of such T cells and the mechanisms responsible for their resistance to depletion are poorly studied. In the present study, we showed that CD4+ T cells that are resistant to polyclonal anti-lymphocyte serum (ALS) mediated depletion exhibit phenotypic features of memory cells and uniformly express OX40 on the cell surface. Studies using the foxp3gfp knockin mice revealed that the remaining CD4+OX40+ cells consist of Foxp3+ Tregs and Foxp3\u2212 T effector\/memory cells. The ALS-resistant CD4+OX40+ cells failed to mediate skin allograft rejection upon adoptive transferring into congenic Rag\u2212\/\u2212 mice, but removal of Foxp3+ Tregs from the OX40+ cells resulted in prompt skin allograft rejection. Importantly, OX40 is critical to survival of both Foxp3+ Tregs and T effector\/memory cells. However, OX40 exhibits opposing effects on the functional status of Foxp3+ Tregs and T effector\/memory cells, as stimulation of OX40 on T effector cells induced amplified cell proliferation but stimulation of OX40 on the Foxp3+ Tregs impaired their suppressor functions. Our study demonstrates that OX40 is a critical molecule in regulating survival and functions of depletion-resistant T cells; and these findings may have important clinical implications.<\/jats:p>","DOI":"10.4049\/jimmunol.179.8.5584","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:19:36Z","timestamp":1397848776000},"page":"5584-5591","source":"Crossref","is-referenced-by-count":56,"title":["OX40 Controls Functionally Different T Cell Subsets and Their Resistance to Depletion Therapy"],"prefix":"10.1093","volume":"179","author":[{"given":"Alexander","family":"Kroemer","sequence":"first","affiliation":[{"name":"Harvard Medical School, Transplant Research Center, Beth Israel Deaconess Medical Center , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Transplant Research Center, Beth Israel Deaconess Medical Center , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh Diem","family":"Vu","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Transplant Research Center, Beth Israel Deaconess Medical Center , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenda","family":"Gao","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Transplant Research Center, Beth Israel Deaconess Medical Center , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Minamimura","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Transplant Research Center, Beth Israel Deaconess Medical Center , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Transplant Research Center, Beth Israel Deaconess Medical Center , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Maki","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Transplant Research Center, Beth Israel Deaconess Medical Center , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian Chang","family":"Li","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Transplant Research Center, Beth Israel Deaconess Medical Center , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,10,15]]},"reference":[{"key":"2026012809270332800_R1","first-page":"103","volume-title":"Transplant. 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