title: The effects of rapamycin on regulatory T cells: its potential time-dependent role in inducing transplant tolerance.
abstract: The immunosuppressive drug rapamycin (RAPA) has been used clinically to prevent graft rejection since 1999 because of its suppressive effects on T cell activation and proliferation. Recently, many studies have suggested that RAPA also has the potential to promote tolerance by driving the expansion of naturally occurring regulatory T (Treg) cells, and facilitating the de novo generation of induced Treg cells, which has aroused great interest in its potential ability to promote tolerance after transplantation. However, its effect on Treg cells remains controversial both in vitro and in vivo. Here, we systematically analyzed data on the effects of RAPA from both clinical and basic studies: (1) To compare its clinical effect with calcineurin inhibitors in transplant recipients, and discuss whether its effects on graft survival correlates with its effects on Treg cells. (2) To analyze the effects of RAPA on Treg cells from animal and in vitro studies, and to investigate whether the effects of RAPA on Treg cells was dependent on dosage and timing. (3) To discuss the mechanisms involved and how they might be applied to induce transplant tolerance.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shan
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China; Chinese Cochrane Centre, Chinese Evidence-Based Medicine Centre, Chengdu 610041, Sichuan Province, PR China. Electronic address: yzmylab@hotmail.com.
authors.forename: Youping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China.
authors.forename: Xuelu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018655:Lymphocyte Count; D016377:Organ Transplantation; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*; D013997:Time Factors; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus
keywords: Rapamycin; Regulatory T cells; Systematic review; Time-dependent effects; Tolerance induction; Transplantation