Schlaak J, Hermann E, Ringhoffer M, Probst P, Gallati H, Meyer zum Büschenfelde K H, Fleischer B
First Department of Medicine, University of Mainz, FRG.
Eur J Immunol. 1992 Nov;22(11):2771-6. doi: 10.1002/eji.1830221103.
The pathogenetic mechanisms underlying the development of reactive arthritis and the functional capacities of synovial T cells specific for Yersinia enterocolitica are still unclear. In this study we have determined the cytokine secretion patterns of 24 CD4+ synovial fluid (SF)-derived T cell clones from 2 patients with Yersinia-induced reactive arthritis, 16 clones specific for different Yersinia antigens and 8 clones as controls. The clones specific for Yersinia antigens predominantly belong to the T helper cell 1 (Th1) subset with production of interferon (IFN)-gamma and interleukin (IL)-2, but no IL-4, whereas SF T cells not reactive with Yersinia antigens produce IL-2, IL-4 and IFN-gamma and thus belonged to the Th0 subset. Moreover, short-term T cell lines established from SF and peripheral blood showed the same pattern. To further analyze the functional relevance of these data we investigated the influence of IFN-gamma and IL-4 on the intracellular killing of Yersinia in a human glioblastoma cell line. Our data show that the Th1 cytokine IFN-gamma promotes intracellular killing of Yersinia, whereas this effect is antagonized by the Th2 cytokine IL-4. Furthermore, the Th2 cytokine IL-10 inhibited the antigen-specific proliferative response and IFN-gamma and IL-2 production by the Th1 cells. These results provide insight into the antibacterial mechanisms at work in reactive arthritis after infection with Yersinia enterocolitica and, for the first time, reveal the cross-regulatory properties of cytokines derived from Th1 and Th2 cells in a human immune response to bacterial antigens.
反应性关节炎发生的致病机制以及小肠结肠炎耶尔森菌特异性滑膜T细胞的功能能力仍不清楚。在本研究中，我们测定了2例耶尔森菌诱导的反应性关节炎患者的24个CD4⁺ 滑膜液（SF）来源的T细胞克隆的细胞因子分泌模式，其中16个克隆对不同的耶尔森菌抗原有特异性，8个克隆作为对照。对耶尔森菌抗原有特异性的克隆主要属于T辅助细胞1（Th1）亚群，产生干扰素（IFN）-γ和白细胞介素（IL）-2，但不产生IL-4，而与耶尔森菌抗原无反应的SF T细胞产生IL-2、IL-4和IFN-γ，因此属于Th0亚群。此外，从SF和外周血建立的短期T细胞系显示出相同的模式。为了进一步分析这些数据的功能相关性，我们研究了IFN-γ和IL-4对人胶质母细胞瘤细胞系中耶尔森菌细胞内杀伤的影响。我们的数据表明，Th1细胞因子IFN-γ促进耶尔森菌的细胞内杀伤，而这种作用被Th2细胞因子IL-4拮抗。此外，Th2细胞因子IL-10抑制Th1细胞的抗原特异性增殖反应以及IFN-γ和IL-2的产生。这些结果为小肠结肠炎耶尔森菌感染后反应性关节炎中的抗菌机制提供了见解，并首次揭示了Th1和Th2细胞来源的细胞因子在人类对细菌抗原免疫反应中的交叉调节特性。
