调节性T细胞在实验性自身免疫性葡萄膜炎中的作用

Role of regulatory T cells in experimental autoimmune uveoretinitis

目的探讨CD4+调节性T细胞(Treg)在实验性自身免疫性葡萄膜炎(EAU)病程进展中的作用。方法通过IRBP161-180和完全弗氏佐剂皮下免疫,在B10RⅢ小鼠诱导产生EAU,对眼内炎症行临床检查并对其严重程度予以评分。通过免疫磁珠分选EAU恢复期小鼠脾脏CD4+T细胞、CD8+T细胞、CD4+CD25+T细胞和CD4+CD25-T细胞。通过流式细胞术分析脾脏CD4+CD25+Foxp3+T细胞的比例。通过体内过继转移评价Treg的抑制效应。结果小鼠诱导EAU后产生眼内炎症反应。将EAU恢复期小鼠脾细胞、脾CD4+T细胞或脾CD4+CD25+T细胞过继转移入正常小鼠继而皮下免疫诱导EAU,眼底检查显示受者小鼠眼内炎症程度明显降低。相反,正常小鼠脾细胞、EAU恢复期脾CD8+T细胞或CD4+CD25-T细胞过继转移无此效应。流式细胞分析显示随着EAU的发展,脾内CD4+CD25+T细胞比例和CD4+CD25+Foxp3+T细胞比例逐步升高,并在恢复期维持较高水平。结论 CD4+Treg随着EAU的病程进展数量增多,它们可能参与EAU的自发缓解。

Objective To investigate the role of CD4^＋ regulaoty T cells（Treg） in the development of experimental autoimmune uveoretinitis（EAU）.Methods EAU was induced in B10RIII mice by subcutaneous immunization of IRBP161-180 in complete Freund＇s adjuvant,and the severity of retinal inflammation was clinically assessed and scored on a 0-5 scale.Magnetic activated cell sorting（MACS） was used to purify CD4^＋T,CD8^＋T,CD4^＋CD25^＋T and CD4^＋CD25^-T cells from post-recovery spleen cells of EAU mice.Flow cytometry was used to analyze the frequency of CD4^＋CD25^＋Foxp3^＋T cells.Adoptive transfer was used to evaluate the suppressive activity of Treg.Results Clinical assessment showed a severe intraocular inflammation in the immunized mice.The fundus examinations showed that the mice injected with post-recovery spleen cells,CD4^＋T cells or CD4^＋CD25^＋T cells had a significant reduction in clinical scores,which reflects a suppressed inflammatory response.The frequency of CD4^＋CD25^＋T cells and CD4^＋CD25^＋Fopx3^＋T cells increased with the development of intraocular inflammation and maintained a high level up to recover.Conclusion A significantly increased frequency and immunoregulatory action of CD4^＋Treg is associated with EAU development and may be involved in the regression of EAU.