Predominance of Th1‐type T cells in synovial fluid of patients with Yersinia‐induced reactive arthritis

Abstract

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 (T_h1) subset with production of interferon (IFN)-γ and interleukin (IL)-2, but no IL-4, whereas SF T cells not reactive with Yersinia antigens produce IL-2, IL-4 and IFN-γ and thus belonged to the T_h0 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-γ and IL-4 on the intracellular killing of Yersinia in a human glioblastoma cell line. Our data show that the T_h1 cytokine IFN-γ promotes intracellular killing of Yersinia, whereas this effect is antagonized by the T_h2 cytokine IL-4. Furthermore, the T_h2 cytokine IL-10 inhibited the antigen-specific proliferative response and IFN-γ and IL-2 production by the T_h1 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 T_h1 and T_h2 cells in a human immune response to bacterial antigens.