{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:08:10Z","timestamp":1791011290810,"version":"4.1.0"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2005,9,1]],"date-time":"2005-09-01T00:00:00Z","timestamp":1125532800000},"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":[[2005,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Previous studies have shown that pretransplant donor lymphocyte infusion (DLI) can enhance xenograft survival. However, the mechanism by which DLI induces xenograft survival remains obscure. Using T cell subset-deficient mice as recipients we show that CD4+, but not CD8+, T cells are necessary to mediate the rejection of concordant cardiac xenografts. Adoptive transfer of naive CD4+ T cells induces rejection of accepted cardiac xenografts in CD4\u2212\/\u2212 mice. This rejection can be prevented by pretransplant DLI in the absence of any other treatment. Furthermore, we demonstrate that DLI activates \u03b1\u03b2-TCR+CD3+CD4\u2212CD8\u2212 double-negative (DN) regulatory T (Treg) cells in xenograft recipients, and that DLI-activated DN Treg cells can inhibit the proliferation of donor-specific xenoreactive CD4+ T cells in vitro. More importantly, adoptive transfer of DLI-activated DN Treg cells from xenograft recipients can suppress the proliferation of xenoreactive CD4+ T cells and their ability to produce IL-2 and IFN-\u03b3 in vivo. Adoptive transfer of DLI-activated DN Treg cells also prevents CD4+ T cell-mediated cardiac xenograft rejection in an Ag-specific fashion. These data provide direct evidence that DLI can activate recipient DN Treg cells, which can induce donor-specific long-term cardiac xenograft survival by suppressing the proliferation and function of donor-specific CD4+ T cells in vivo.<\/jats:p>","DOI":"10.4049\/jimmunol.175.5.3409","type":"journal-article","created":{"date-parts":[[2014,4,24]],"date-time":"2014-04-24T13:44:04Z","timestamp":1398347044000},"page":"3409-3416","source":"Crossref","is-referenced-by-count":50,"title":["Donor Lymphocyte Infusion Induces Long-Term Donor-Specific Cardiac Xenograft Survival through Activation of Recipient Double-Negative Regulatory T Cells"],"prefix":"10.1093","volume":"175","author":[{"given":"Wenhao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose R","family":"Torrealba","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas K","family":"Waddell","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Immunology, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,9,1]]},"reference":[{"key":"2025032705415568900_R1","first-page":"437","volume-title":"Immunity","year":"2001"},{"key":"2025032705415568900_R2","first-page":"433","volume-title":"Annu. 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Med.","year":"2002"},{"key":"2025032705415568900_R29","first-page":"3408","volume-title":"Blood","year":"2002"},{"key":"2025032705415568900_R30","first-page":"2828","volume-title":"Blood","year":"2005"},{"key":"2025032705415568900_R31","first-page":"199","volume-title":"Nat. Rev. Immunol.","year":"2003"},{"key":"2025032705415568900_R32","first-page":"399","volume-title":"Immunity","year":"2001"},{"key":"2025032705415568900_R33","first-page":"762","volume-title":"Transplantation","year":"2004"},{"key":"2025032705415568900_R34","first-page":"5558","volume-title":"J. Immunol.","year":"2002"},{"key":"2025032705415568900_R35","first-page":"107","volume-title":"J. Immunol.","year":"2001"},{"key":"2025032705415568900_R36","first-page":"2577","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2001"},{"key":"2025032705415568900_R37","first-page":"1846","volume-title":"J. 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