天花粉蛋白合成肽通过诱导CD8抑制性T细胞治疗实验性自身反应性脑脊髓炎

为了探讨天花粉蛋白合成肽(M-Tk)治疗实验性自身反应性脑脊髓炎(EAE)的可能性及其作用机制,应用自身抗原MBP衍生肽MOG35-55免疫C57BL/6小鼠成功地诱发EAE后,以流式细胞术测定小鼠淋巴结细胞及脾细胞T亚群及细胞因子的表达,并通过临床评分观察M-Tk治疗EAE的有效性,包括以HE和LFB染色观察髓鞘病变。结果发现,M-Tk可抑制MOG35-55特异性T细胞的增殖反应,选择性诱导CD8+CD28-T调节细胞的扩增,明显提高IL-10的分泌和降低IFN-γ的产生,并有效改善EAE小鼠神经功能评分。采用M-Tk诱导的CD8 T细胞作体内输注可取得相似甚至更好的治疗效果(P>0.01)。提示M-Tk在体内诱导产生CD8+CD28-抑制性T细胞并上调IL-10分泌降低IFN-γ产生,是对EAE取得疗效的关键。

Effect of Trichosanthin-derived peptide on activating CD8 regulatory T cells to treat experimental autoimmune encephalomyelitis

M-Tk is a synthesized Trichosanthin-related peptide with suppressive property.To explore the therapeutic effects of M-Tk on experimental autoimmune encephalomyelitis(EAE),the disease was induced in C57BL/6 mouse by the autoimmune antigen MBP-derived peptide MOG35-55.The effects of M-Tk on the differentiation of T subsets and on the secretion levels of cytokines of the lymph node cells and splenocytes in EAE mice were examined.It was showed that M-Tk was active in suppression of MOG-specific T proliferation,in inducing regulatory CD8+CD28-T cells preferentially,in alteration of secreting patterns of IL-10 and IFN-γ,as well as in improving the clinic scores of neurological signs.Moreover,better results of the disease treatment were recorded when M-Tk was substituted with the M-Tk-induced CD8-positive T suppressor cells for in vivo injection(P<0.01).This indicates that the therapeutic effects of M-Tk on EAE is dependent on the generation of CD8+CD28-regulatory T cells in context with up-regulation of IL-10 secretion and down-regulation of IFN-γ production.