The Impact Of Rapamycin On Chemotaxis Of Regulatory T Cells Induced By Allogeneic Antigen

Objective: To investigate the impact of rapamycin on chemotaxis of regulatory T cells induced by allogeneic antigen. Methods: After preparing the skin-antigen of C57BL/6 mice, Balb/c mice were divided into 4 groups, including skin-antigen(s Ag), rapamycin(Rapa), s Ag+Rapa and normal saline(NS), which were induced by intraperitoneal injection with s Ag、Rapa、s Ag+Rapa and NS respectively. The number and expression of chemokine receptors and CD62 L on CD4+CD25-T cells and CD4+CD25+CD127-T cells in peripheral blood were detected with flow cytometer every week during 4-week-induction. The chemotactic effects of CCL4 and CCL22 on CD4+T cells subsets were tested by chemotaxis assay of mononuclear cells which were isolated from spleens of each group mice. Results: ①The number of regulatory cells(Treg) in the first of 3 groups were higher than NS group. However, the trend were varied from groups at different week.The counts of Treg peaked at 1st week in s Ag group, 2nd week in s Ag+Rapa group, 3rd week in Rapa group.②The expression of CCR4 on CD4+CD25+CD127-T cells were highest at 3rd week in group s Ag+Rapa and 4th week in group s Ag(P<0.01). The CCR5 expression at 3rd week in group s Ag was significant higher than others(P<0.05). And the expression of CXCR3 was higher at the first two weeks in Rapa group(P<0.01). The expression of CD62 L on CD4+CD25+CD127-T cells was highest at 4th week in group Rapa compared to other groups, and 2nd week in group s Ag+Rapa was followed. ③Regulated by CCL22, the chemotactic index of CD4+CD25+CD127-T cells was highest at 1st week in group s Ag(P<0.01),while group Rapa and s Ag+Rapa were peaked at 3rd week. The same case went with group Rapa when regulated by CCL4. Conclusion: ①Both rapamycin and skin-antigen could improve the number of Treg cells. Rapamycin may play an important role in kinetics of the changes of number of antigen-specific Treg cells. ②Rapamycin could exert an influence on chemokinereceptors which may have an association with the chemotaxis of Treg cells. ③The chemotaxis effects of CCL4 and CCL22 on CD4+CD25+CD127-T cells were changed with time and were somewhat out of sync with corresponding chemokine receptors expression which indicated that the chemotaxis effect may depend on the Treg cells counts and state of chemokine receptor.