Bettelli E, Das M P, Howard E D, Weiner H L, Sobel R A, Kuchroo V K
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Immunol. 1998 Oct 1;161(7):3299-306.
Experimental autoimmune encephalomyelitis (EAE) and other organ-specific autoimmune diseases are induced by autoantigen-specific Th1 cells. In contrast, transfer of autoantigen-reactive Th2 cells that produce IL-4 and IL-10 can prevent and/or reverse EAE. The relative roles of these two Th2 cytokines in the regulation of EAE has not been evaluated. Utilizing IL-4 and IL-10 knockout mice deficient for these cytokines and IL-10 and IL-4 transgenic mice overexpressing these cytokines, we demonstrate that IL-10-deficient mice (IL-10(-/-)) are more susceptible and develop a more severe EAE when compared with IL-4-deficient mice (IL-4(-/-)) or wild-type mice. T cells from IL-10(-/-) mice exhibit a stronger Ag-specific proliferation, produce more proinflammatory cytokines (IFN-gamma and TNF-alpha) when stimulated with an encephalitogenic peptide, and induce very severe EAE upon transfer into wild-type mice. In contrast, while IL-4 transgenic mice develop similar disease compared with their nontransgenic littermates, mice transgenic for IL-10 are completely resistant to the development of EAE. Taken together, our data suggest that IL-10 plays a more critical role in the regulation of EAE by regulating autopathogenic Th1 responses.
实验性自身免疫性脑脊髓炎（EAE）和其他器官特异性自身免疫性疾病是由自身抗原特异性Th1细胞诱导产生的。相比之下，产生白细胞介素-4（IL-4）和白细胞介素-10（IL-10）的自身抗原反应性Th2细胞的转移可以预防和/或逆转EAE。这两种Th2细胞因子在EAE调节中的相对作用尚未得到评估。利用缺乏这些细胞因子的IL-4和IL-10基因敲除小鼠以及过表达这些细胞因子的IL-10和IL-4转基因小鼠，我们证明与IL-4基因敲除小鼠（IL-4(-/-)）或野生型小鼠相比，IL-10基因敲除小鼠（IL-10(-/-)）更易患EAE，且病情更严重。来自IL-10(-/-)小鼠的T细胞表现出更强的抗原特异性增殖，在用致脑炎肽刺激时产生更多的促炎细胞因子（干扰素-γ和肿瘤坏死因子-α），并在转移到野生型小鼠后诱导出非常严重的EAE。相比之下，虽然IL-4转基因小鼠与其非转基因同窝小鼠相比患类似疾病，但IL-10转基因小鼠对EAE的发生完全具有抗性。综上所述，我们的数据表明IL-10通过调节自身致病性Th1反应在EAE的调节中发挥更关键的作用。
