Combination of rapamycin and IL-2 do not affect antigen presentation ability of rat B cell and could promote Tregs proliferation and inhibitory activity.
Rapamycin (RPM), a powerful agent used clinically in transplant recipients, induces CD4(+)CD25(+) regulatory T cells (Tregs) which play an important role in induction of immune tolerance. However, long-term use of RPM has negative side effects. In this report, we found that combination with the low dose RPM and high dose IL-2 did not affect antigen presentation of rat B cells to Tregs, and could efficiently promote Tregs proliferation and enhance their inhibitory activities in vitro. In addition, the combination of low dose RPM and high dose IL-2 enhanced mRNA expression of Foxp3, TGF-beta1 and Pim-2 in Tregs but not in CD4(+)CD25(-) T effector cells (Teffs). The Tregs inhibitory activity is positively associated with mRNA expressions of TGF-beta1 and Pim-2 while unrelated to the Foxp3 mRNA expression. Our present study offers one approach to expand functional Tregs in vitro, which maybe used for clinical immune tolerance induction.
Zhang
Chuntao
C
Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan Province, People's Republic of China.
Shan
Juan
J
Lu
Jun
J
Huang
Yuchuan
Y
Feng
Li
L
Long
Dan
D
Li
Shengfu
S
Li
Quansheng
Q
Li
Youping
Y
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015704:CD4 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000008:administration & dosage*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D020123:Sirolimus / Q000008:administration & dosage*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053773:Transforming Growth Factor beta1; D020123:Sirolimus