Institute for Immunology, Ludwig Maximilian University, 80336 Munich, Germany.
J Immunol. 2012 Jan 15;188(2):615-23. doi: 10.4049/jimmunol.1101164. Epub 2011 Dec 7.
Stimulation of the immune system by pathogens, allergens, or autoantigens leads to differentiation of CD4(+) T cells with pro- or anti-inflammatory effector cell functions. Based on functional properties and expression of characteristic cytokines and transcription factors, effector CD4(+) T cells have been grouped mainly into Th1, Th2, Th17, and regulatory T (Treg) cells. At least some of these T cell subsets remain responsive to external cues and acquire properties of other subsets, raising the hope that this functional plasticity might be exploited for therapeutic purposes. In this study, we used an Ag-specific adoptive transfer model and determined whether in vitro-polarized or ex vivo-isolated Th1, Th17, or Treg cells can be converted into IL-4-expressing Th2 cells in vivo by infection of mice with the gastrointestinal helminth Nippostrongylus brasiliensis. Th1 and Th17 cells could be repolarized to acquire the expression of IL-4 and lose the expression of their characteristic cytokines IFN-γ and IL-17A, respectively. In contrast, both in vitro-generated and ex vivo-isolated Treg cells were largely resistant to repolarization. The helminth-induced conversion of Th1 or Th17 cells into Th2 cells may partially explain the inverse correlation between helminth infection and protection against autoimmune disorders.
病原体、过敏原或自身抗原刺激免疫系统，导致 CD4(+) T 细胞分化为具有促炎或抗炎效应细胞功能的细胞。基于功能特性和特征细胞因子和转录因子的表达，效应 CD4(+) T 细胞主要分为 Th1、Th2、Th17 和调节性 T（Treg）细胞。至少其中一些 T 细胞亚群仍然对外界信号有反应，并获得其他亚群的特性，这增加了一种希望，即这种功能可塑性可能被用于治疗目的。在这项研究中，我们使用了 Ag 特异性过继转移模型，并确定了体内感染胃肠道蠕虫旋毛虫巴西种的小鼠是否可以将体外极化或体外分离的 Th1、Th17 或 Treg 细胞转化为表达 IL-4 的 Th2 细胞。Th1 和 Th17 细胞可以被重新极化以获得 IL-4 的表达，并分别失去其特征细胞因子 IFN-γ 和 IL-17A 的表达。相比之下，体外生成和体外分离的 Treg 细胞对重新极化的抵抗力很大。蠕虫诱导的 Th1 或 Th17 细胞向 Th2 细胞的转化可能部分解释了蠕虫感染与自身免疫性疾病保护之间的反比关系。
