{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:46:54Z","timestamp":1791920814177,"version":"4.3.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2007,8,1]],"date-time":"2007-08-01T00:00:00Z","timestamp":1185926400000},"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":[[2007,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We have previously shown that pretransplant donor lymphocyte infusion (DLI) together with transient depletion of CD4+ T cells could induce permanent rat-to-mouse heart graft survival, whereas depleting CD4+ T cells alone failed to do so. In this study, we investigated the mechanism leading to long-term xenograft survival. We found that peripheral CD4+ T cells from DLI\/anti-CD4-treated mice could mount rat heart graft rejection after adoptive transfer into B6 CD4\u2212\/\u2212 mice. Infusing donor-Ag-loaded mature dendritic cells (DCs) could break long-term cardiac xenograft survival in DLI\/anti-CD4-treated mice. Interestingly, when the number and phenotype of graft-infiltrating cells were compared between anti-CD4- and DLI\/anti-CD4-treated groups, we observed a significant increase in both the number and suppressive activity of \u03b1\u03b2-TCR+CD3+CD4\u2212CD8\u2212 double negative regulatory T cells and decrease in the numbers of CD4+ and CD8+ T cells in the xenografts of DLI\/anti-CD4-treated mice. Moreover, there was a significant reduction in MHC class II-high DCs within the xenografts of DLI\/anti-CD4-treated recipients. DCs isolated from the xenografts of anti-CD4- but not DLI\/anti-CD4-treated recipients could stimulate CD4+ T cell proliferation. Our data indicate that functional anti-donor T cells are present in the secondary lymphoid organs of the mice that permanently accepted cardiac xenografts. Their failure to reject xenografts is associated with an increase in double negative regulatory T cells as well as a reduction in Ag stimulation by DCs found within grafts. These findings suggest that local regulatory mechanisms need to be taken into account to control anti-xenograft T cell responses.<\/jats:p>","DOI":"10.4049\/jimmunol.179.3.1542","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T22:56:47Z","timestamp":1397861807000},"page":"1542-1548","source":"Crossref","is-referenced-by-count":16,"title":["Both Infiltrating Regulatory T Cells and Insufficient Antigen Presentation Are Involved in Long-Term Cardiac Xenograft Survival"],"prefix":"10.1093","volume":"179","author":[{"given":"Wenhao","family":"Chen","sequence":"first","affiliation":[{"name":"Toronto General Research Institute, University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto , Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Diao","sequence":"additional","affiliation":[{"name":"Toronto General Research Institute, University Health Network , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislaw M","family":"Stepkowski","sequence":"additional","affiliation":[{"name":"Division of Immunology and Organ Transplantation, University of Texas Medical School at Houston , Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Toronto General Research Institute, University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Laboratory Medicine and Pathobiology, University of 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":[[2007,8,1]]},"reference":[{"key":"2025032701455234300_R1","first-page":"437","volume-title":"Immunity","year":"2001"},{"key":"2025032701455234300_R2","first-page":"433","volume-title":"Annu. 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