{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:11:10Z","timestamp":1777957870791,"version":"3.51.4"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Objective<\/jats:title>\n \n Regulatory T cells (Tregs) play an essential role in transplantation immune tolerance. Although CD4\n +<\/jats:sup>\n Tregs have been extensively studied, the contribution of CD8\n +<\/jats:sup>\n regulatory T-cell subsets to transplant tolerance remains less well defined. This study aimed to characterize Treg subsets associated with immune tolerance in a rat liver transplantation model and in liver transplant recipients.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Mesenchymal stem cell-derived tolerogenic dendritic cells (tolDCs) were adoptively infused in a rat liver transplantation model. The frequencies of CD4\n +<\/jats:sup>\n Foxp3\n +<\/jats:sup>\n Tregs and CD8\n +<\/jats:sup>\n CD45RC\n low\/-<\/jats:sup>\n Tregs in peripheral blood, spleen, and graft tissue were analyzed by flow cytometry and multiplex immunofluorescence. Peripheral blood samples from liver transplant recipients with long-term stable graft function or acute rejection were also analyzed.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Adoptive infusion of tolDCs significantly prolonged graft survival in the rat liver transplantation model. Increased frequencies of CD4\n +<\/jats:sup>\n Foxp3\n +<\/jats:sup>\n Tregs and CD8\n +<\/jats:sup>\n CD45RC\n low\/-<\/jats:sup>\n Tregs were observed in peripheral blood, spleen, and graft tissue in tolDC-induced and spontaneous tolerant animals. MHC-II\n +<\/jats:sup>\n CD8\n +<\/jats:sup>\n CD45RC\n low\/-<\/jats:sup>\n Tregs were enriched within tolerant grafts, suggesting an association with local immune regulation. In liver transplant recipients, the frequency of peripheral CD8\n +<\/jats:sup>\n CD45RC\n low\/-<\/jats:sup>\n Tregs was higher in patients with long-term stable graft function than in patients with acute rejection\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n CD8\n +<\/jats:sup>\n CD45RC\n low\/-<\/jats:sup>\n Tregs are associated with transplantation immune tolerance and may cooperate with CD4\n +<\/jats:sup>\n Foxp3\n +<\/jats:sup>\n Tregs in maintaining a tolerant immune microenvironment.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1829051","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:17:15Z","timestamp":1777954635000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CD8 regulatory T cells are a novel type regulatory T cells in the induction of transplantation immune tolerance"],"prefix":"10.3389","volume":"17","author":[{"given":"Jin-can","family":"Huang","sequence":"first","affiliation":[{"name":"Devision of Hepatobiliary and Pancreaticosplenic Surgery, Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Devision of Hepatobiliary and Pancreaticosplenic Surgery, Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-di","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, The First Medical Center, Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Xia","sequence":"additional","affiliation":[{"name":"Zhantansi Department, Central Medical Branch of PLA General Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo-sheng","family":"Du","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, General Hospital of Northern Theater Command","place":["Shenyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren","family":"Lang","sequence":"additional","affiliation":[{"name":"Devision of Hepatobiliary and Pancreaticosplenic Surgery, Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Devision of Hepatobiliary and Pancreaticosplenic Surgery, Department of General 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