{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:25:35Z","timestamp":1773660335426,"version":"3.50.1"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2003,2,1]],"date-time":"2003-02-01T00:00:00Z","timestamp":1044057600000},"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":[[2003,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A novel subset of CD3+CD4\u2212CD8\u2212 (double negative; DN) regulatory T cells has recently been shown to induce donor-specific skin allograft acceptance following donor lymphocyte infusion (DLI). In this study, we investigated the effect of DLI on rat to mouse cardiac xenotransplant survival and the ability of DN T cells to regulate xenoreactive T cells. B6 mice were given either DLI from Lewis rats, a short course of depleting anti-CD4 mAb, both DLI and anti-CD4 treatment together, or left untreated. DLI alone did not prolong graft survival when compared with untreated controls. Although anti-CD4-depleting mAb alone significantly prolonged graft survival, grafts were eventually rejected by all recipients. However, the combination of DLI and anti-CD4 treatment induced permanent cardiac xenograft survival. We demonstrate that recipients given both DLI and anti-CD4 treatment had a significant increase in the total number of DN T cells in their spleens when compared with all other treatment groups. Furthermore, DN T cells harvested from the spleens of DLI plus anti-CD4-treated mice could dose-dependently inhibit the proliferation of syngeneic antidonor T cells. Suppression mediated by these DN T cells was specific for antidonor T cells as T cells stimulated by third-party Ags were not suppressed. These results demonstrate for the first time that a combination of pretransplant DLI and anti-CD4-depleting mAb can induce permanent survival of rat to mouse cardiac xenografts and that DN T regulatory cells play an important role in preventing long-term concordant xenograft rejection through the specific suppression of antidonor T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.170.4.1846","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T19:49:07Z","timestamp":1398109747000},"page":"1846-1853","source":"Crossref","is-referenced-by-count":56,"title":["Role of Double-Negative Regulatory T Cells in Long-Term Cardiac Xenograft Survival"],"prefix":"10.1093","volume":"170","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, University of Toronto , Toronto ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan S","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network, University of Toronto , Toronto ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin J","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network, University of Toronto , Toronto ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myron I","family":"Cybulsky","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network, University of Toronto , Toronto ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, University of Toronto , Toronto ,","place":["Canada"]},{"name":"Department of Immunology, University of Toronto , Toronto ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2003,2,15]]},"reference":[{"key":"2026020210120345500_R1","first-page":"437","volume-title":"Immunity","year":"2001"},{"key":"2026020210120345500_R2","first-page":"433","volume-title":"Annu. 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