Mechanisms of immune suppression for activated T cells by infliximab therapy in patients with Behcet's uveoretinitis.

以往的研究表明，白塞病(BD)的眼内炎症以Th1和Th17免疫反应为主。最近，Th22细胞被确定为与自身免疫性疾病相关的一种新的Th谱系。我们发现，从BD患者的眼睛样本中建立的Th22型T细胞克隆可以产生大量的Th22相关细胞因子IL-22和肿瘤坏死因子-α。BD患者外周血中的CD4+T细胞可分化为Th22细胞。抗肿瘤坏死因子-α抗体英夫利昔单抗体外作用于Th22细胞后，不能产生IL-22。此外，从实验性自身免疫性葡萄膜炎(EAU)小鼠身上分离出Th22细胞，EAU是BD的动物模型，EAU的眼内T细胞在视网膜抗原存在的情况下产生大量IL-22。提示Th22细胞在BD眼部炎症中可能起关键作用。英夫利昔单抗抑制Th22细胞可保护BD葡萄膜炎患者免受严重眼部炎症的侵袭。

Previous studies suggested that the intraocular inflammation in Behcet’s disease (BD) is predominated by Th1 and Th17 immune responses. Recently, Th22 cells were identified as a novel Th lineage associated with autoimmune diseases. We showed that Th22-type T cell clones established from ocular samples from patients with BD produced large amounts ofTh22 associated cytokines IL-22 and TNF-α. CD4+ T cells from PBMCs of BD patients differentiated into Th22 cells. Th22 cells exposed to infliximab, anti-TNF-αantibody, in vitro failed to produce IL-22. Moreover, Th22 cells were isolated from mice with experimental autoimmune uveitis (EAU), an animal model of BD, and intraocular T cells from EAU produced large amounts of IL-22 in the presence of retinal antigens. Theseresults suggest that Th22 cells may play a key role in the ocular inflammation in BD. Suppression of Th22 cells by infliximab may protect uveitis patients with BD from severe ocular inflammation.