Rapamycin promotes the expansion of CD4(+) Foxp3(+) regulatory T cells after liver transplantation.
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.
Lu
L
L
Division of Liver Transplantation Center, Nanjing Medical University, Nanjing, China.
Qian
X F
XF
Rao
J H
JH
Wang
X H
XH
Zheng
S G
SG
Zhang
F
F
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*
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus