[Effect of Rapamycin on CD4(+) CD25(+) regulatory T cells in allo-transplantation tolerance model].
OBJECTIVE
To study the effect of Rapamycin(Rapa) on CD4(+) CD25(+) regulatory T cells in allo-transplantation tolerance model.


METHODS
The model of skin allo-transplantation was established. The recipient BALB/c mice were injected with allogeneic donor spleen cells from B6 on the day before grafting and with cyclosporine(CsA) after transplantation. T cells were purified on the day 14 from the tolerant group and cultured with Rapa and/or IL-2 in different concentrations in vitro. Mixed lymphocyte reaction (MLR) was used to analyze the specific recall reaction of T cells. Percentages of CD4(+) CD25(+) regulatory T cells were examined by flow cytometry (FCM). The expression of Foxp3 mRNA was measured by RT-PCR, and the level of IL-10 in supernatant of T cells cultured in vitro was determined by ELISA. BALB/c-SCID mice underwent allo-transplantation were given adoptive transfer of T cells treated with Rapa and/or IL-2, then the survival conditions of the grafted skin were observed daily.


RESULTS
CsA plus donor splenocyte injection can prolong allograft of BALB/c significantly (P<0.05). The number of CD4(+) CD25(+) regulatory T cells and the expression of Foxp3 mRNA for T cell in the tolerant group treated with Rapa and/or IL-2 were obviously increased. Adoptive transfusion of T cells from tolerant mice treated with IL-2/Rapa obviously prolonged the allograft survival time in allografted-SCID mice.


CONCLUSIONS
Rapa can increase the ratio of CD4(+) CD25(+) regulatory T cells in vitro and prolong the graft survival time obviously after adoptive immunity, and these effects are enhanced by low-dose of IL-2.
Zheng
Yong-Xian
YX
Institute of Experimental Nuclear Medicine, Medical School of Shandong University, Jinan 250012, China.
Hou
Gui-Hua
GH
Song
Jing
J
Zhang
Chao
C
Liang
Ting
T
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D020123:Sirolimus / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology*
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D020123:Sirolimus