西罗莫司和环孢素A对Th17细胞和调节性T淋巴细胞分化影响的比较

Effects of sirolimus vs cyclosporine A on in vitro differentiation of Th17 cells and T regulatory cells

目的比较西罗莫司（SRL）和环孢素A（CsA）对体外诱导CD4^＋T淋巴细胞向Th17和调节性T淋巴细胞分化的影响。方法使用抗CD3和抗CD28单克隆抗体（简称抗CD3单抗和抗CD28单抗）刺激CD4^＋T淋巴细胞，并在培养体系中分别加入转化生长因子β（TGF-β）；TGF-β＋白细胞介素6（IL-6）；TGF-β＋IL-6＋SRL；TGF-β＋IL-6＋CsA。72h后用流式细胞术检测细胞内Foxp3和IL-17的表达水平，观察CD4^＋T淋巴细胞的分化情况及SRL和CsA对CD4^＋T淋巴细胞体外分化的影响。结果在经抗CD3单抗和抗CD28单抗刺激后，TGF-β可诱导Foxp3^＋细胞（调节性T淋巴细胞，Treg）的增殖与分化，而TGF-β＋IL6可诱导Th17细胞的增殖与分化。在培养体系中加入SRL和CsA，均可使Th17细胞的增殖与分化减少；SRL可促进Treg的增殖与分化，而CsA抑制Treg的增殖与分化。结论SRL可以促进CD4^＋T淋巴细胞向Treg增殖与分化，而抑制Th17细胞的增殖与分化；CsA既抑制Treg的增殖与分化，又抑制Th17细胞的增殖与分化。

Objective To compare the effects of sirolimus （SRL） vs cyclosporine A （CsA） on in vitro differentiation of regulatory T cells and Th17 cells. Methods CD4^＋ T cells sorted by FACS were stimulated with anti-CD3 antibody （Ab）, anti-CD28Ab and TGF-β, in the presence or absence of IL6. Flow cytometry was used to detect the expression of Foxp3 and IL-17 72 h after stimulation. And SLR or CsA was added to the medium with different concentrations to estimate the effects on differentiation of CD4^＋ T cells. Results After being stimulated with anti CD3 Ab and Anti-CD28 Ab, TGF-β mediated generation of T regulatory cells and TGF-β/IL-6 induced generation of Th17 cells. SRL and CsA potently inhibited the TGF-β and IL-6-induced generation of IL-17-producing cells. Intriguingly, SRL promoted, while CsA markedly inhibited, TGF-β mediated generation of T regulatory cells. Conclusion The capacity of SRL to generate immunosuppressive Tregs and to suppress differentiation of pathogenic Th17 cells furthers our understanding of the basis for the therapeutic immunosuppressive effects of SRL in patients with autoimmune diseases and allotransplantation reactions.