临床主流免疫抑制剂对辅助性T细胞17的影响和机制

Effects and mechanisms of immunosuppressants on development of murine T helper cell 17

目的观察在体外及体内环境下，免疫抑制剂对小鼠辅助性T细胞17（Thl7）分化增殖的影响。方法小鼠脾脏初始CD4^＋CD25-T淋巴细胞使用抗CD3抗体及抗CD28抗体活化，转化生长因子-β1（TGF-β1）及白细胞介素-6（IL-6）等因子诱导，促使其向Thl7细胞方向分化；分组施加不同剂量的免疫抑制剂进行干预。流式细胞仪检测各组CD4^＋Thl7细胞纯度，反转录一聚合酶链反应（RT-PCR）及Westernblot检测各组IL-17mRNA相对量。并建立小鼠颈部心脏移植模型，研究免疫抑制剂对小鼠Thl7细胞及细胞因子的影响。结果在体外和体内环境下，Thl7细胞的分化增殖受到免疫抑制剂的抑制；同时，小鼠心脏的急性排斥反应也得到了控制。临床常用免疫抑制剂可抑制小鼠Thl7细胞的分化增殖，呈剂量依赖性：相对值在他克莫司各组间差异有统计学意义（t=5．357、7．572、8．251，P=0．038、0．029、0．021），在西罗莫司各组间差异有统计学意义（t=4．896、6．772、7．837，P=0．042、0．037、0．033）。结论免疫抑制剂可以抑制Thl7细胞的分化增殖。

Objective In vitro and in vivo, to examine the effects of immunosuppressants on the differentiation and proliferation of mice T helper cell 17 （Thl7） cells. Methods Murine naive CIM ＋ CD25 - T cells were stimulated with plate - bound anti - CD3 and anti - CD28 ; then were induced by the cytokines such as transforming growth factor - βl （ TGF - β1 ） and intedeukin - 6 （ IL - 6 ） , etc. Immuno- suppressant was added to the cells at the desired time point and desired concentrations. The subsets of CD4 ＋ Thl7 cells were examined by flow cytometry. The expression of IL - 17 mRNA was assayed by RT - polymerase chain reaction （ RT - PCR） and Western blotting. Besides, to investigate the role of Thl7 cells and their cytokines in cardiac allrft rejection in mice. Results In vitro and in vivo, immunosuppressant inhibit the differentiation and proliferation of Th17 cells in a dose -dependent manner; and allograft rejec- tion was suppressed. The RQ differences among the FKS06 - groups are considered significant （ t = 5. 357, 7. 572, 8. 251, P =0. 038, 0. 029, 0. 021 ） ; the differences among the SRL - groups are considered signif- icant （t =4. 896, 6. 772, 7. 837, P = 0. 042, 0. 037, 0. 033）. Conclusion Immunosuppressants can in- hibit the differentiation and poliferation of Thl7 cells.