Critical role of M. tuberculosis for dendritic cell maturation to induce collagen‐induced arthritis in H‐2b background of C57BL/6 mice

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Abstract
Summary: Collagen‐induced arthritis (CIA) can be induced even in CIA‐resistant H‐2b background of C57BL/6 mice when these mice are immunized with type II collagen (CII) emulsified in complete Freund's adjuvant (CFA) containing high, but not low, dose of Mycobacterium tuberculosis. Here, we investigated the pathogenesis of CIA in C57BL/6 mice induced by the immunizing protocol. We examined expressions of cytokines, costimulatory molecules and major histocompatibility complex (MHC) class II in draining lymph nodes (DLN) in CIA‐induced C57BL/6 mice by quantitative reverse transcription–polymerase chain reaction. We also examined an effect of M. tuberculosis on the expression of these molecules on dendritic cells (DC) in vitro by flow cytometry. We finally examined an effect of M. tuberculosis in CFA used for immunization with CII antigen on priming of CD4+ helper T cells specific to CII in DLN of CIA‐induced C57BL/6 mice. The expression of interferon‐γ (IFN‐γ), Interleukin‐12p40 (IL‐12p40), costimulatory molecules CD40, CD80 and CD86 and MHC class II were up‐regulated in DLN of CIA‐induced C57BL/6 mice. Expressions of these costimulatory molecules were also up‐regulated on DC after stimulation with high, but not low, dose of M. tuberculosis in vitro. Furthermore, priming of CD4+ helper T cells specific to CII antigen in DLN required immunization with CII using CFA containing high, but not low, dose of M. tuberculosis. These results suggested that high dose of M. tuberculosis were required for maturation of DC enough to prime CD4+ helper T cells specific to CII antigen in DLN of H‐2b background of C57BL/6 mice.