Stummvoll Georg H, DiPaolo Richard J, Huter Eva N, Davidson Todd S, Glass Deborah, Ward Jerrold M, Shevach Ethan M
Laboratory of Immunology, Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2008 Aug 1;181(3):1908-16. doi: 10.4049/jimmunol.181.3.1908.
Th cells can be subdivided into IFN-gamma-secreting Th1, IL-4/IL-5-secreting Th2, and IL-17-secreting Th17 cells. We have evaluated the capacity of fully differentiated Th1, Th2, and Th17 cells derived from a mouse bearing a transgenic TCR specific for the gastric parietal cell antigen, H(+)K(+)-ATPase, to induce autoimmune gastritis after transfer to immunodeficient recipients. We have also determined the susceptibility of the disease induced by each of the effector T cell types to suppression by polyclonal regulatory T cells (Treg) in vivo. Each type of effector cell induced autoimmune gastritis with distinct histological patterns. Th17 cells induced the most destructive disease with cellular infiltrates composed primarily of eosinophils accompanied by high levels of serum IgE. Polyclonal Treg could suppress the capacity of Th1 cells, could moderately suppress Th2 cells, but could suppress Th17-induced disease only at early time points. The major effect of the Treg was to inhibit the expansion of the effector T cells. However, effector cells isolated from protected animals were not anergic and were fully competent to proliferate and produce effector cytokines ex vivo. The strong inhibitory effect of polyclonal Treg on the capacity of some types of differentiated effector cells to induce disease provides an experimental basis for the clinical use of polyclonal Treg in the treatment of autoimmune disease in humans.
辅助性T细胞可细分为分泌干扰素-γ的Th1细胞、分泌白细胞介素-4/白细胞介素-5的Th2细胞和分泌白细胞介素-17的Th17细胞。我们评估了源自一只携带针对胃壁细胞抗原H(+)K(+)-ATP酶的转基因TCR的小鼠的完全分化的Th1、Th2和Th17细胞在转移至免疫缺陷受体后诱导自身免疫性胃炎的能力。我们还确定了每种效应T细胞类型所诱导的疾病在体内被多克隆调节性T细胞（Treg）抑制的易感性。每种效应细胞类型都诱导出具有不同组织学模式的自身免疫性胃炎。Th17细胞诱导的疾病破坏性最强，细胞浸润主要由嗜酸性粒细胞组成，并伴有高水平的血清IgE。多克隆Treg可以抑制Th1细胞的能力，可以适度抑制Th2细胞，但仅在早期时间点可以抑制Th17诱导的疾病。Treg的主要作用是抑制效应T细胞的扩增。然而，从受保护动物中分离出的效应细胞没有无反应性，并且在体外具有充分的增殖和产生效应细胞因子的能力。多克隆Treg对某些类型的分化效应细胞诱导疾病的能力具有强大的抑制作用，为多克隆Treg在人类自身免疫性疾病治疗中的临床应用提供了实验依据。
