title: Rapamycin promotes the expansion of CD4(+) Foxp3(+) regulatory T cells after liver transplantation.
abstract: Rapamycin can promote the generation and homeostasis of CD4(+)Foxp3(+) regulatory T cells (Tregs) both in vitro and in vivo. The mechanisms by which rapamycin mediates this effect are poorly defined. In this study, we characterized CD4(+)Foxp3(+) Tregs in liver grafts and peripheral blood following rapamycin treatment using a syngeneic liver transplant model. Orthotopic liver transplantation was performed from Lewis (LEW) to LEW rats. In the first 2 weeks the percentage of CD4(+)Foxp3(+) Tregs was increased in the liver grafts and blood only among the rapamycin group compared with control group. Conversely, the percentage of CD4(+)Foxp3(+) Tregs in the liver graft and blood decreased in the cyclosporine group. In normal rats, rapamycin did not impact the generation of CD4(+)Foxp3(+) Tregs in the thymus. Thus, rapamycin can significantly enhance the percentages of CD4(+)Foxp3(+) Tregs in the thymus and periphery, indicating that rapamycin favors Tregs expansion and may suppress other CD4(+) T cells.
authors.affiliation: Division of Liver Transplantation Center, Nanjing Medical University, Nanjing, China.
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: X F
authors.initials: XF
authors.lastname: Qian
authors.forename: J H
authors.initials: JH
authors.lastname: Rao
authors.forename: X H
authors.initials: XH
authors.lastname: Wang
authors.forename: S G
authors.initials: SG
authors.lastname: Zheng
authors.forename: F
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D020123:Sirolimus / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus