Data from: Regulatory CD4+CD25+ T cells dampen inflammatory disease in murine mycoplasma pneumonia and promote IL-17 AND IFN-? responses
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Mycoplasmas cause respiratory diseases characterized by persistent infection and chronic airway inflammation. Mycoplasma lung disease is immunopathologic, with CD4+ Th cells determining both disease severity and resistance to infection. Th2 cell responses promote immunopathology, while Th1 cells confer resistance to infection. However, regulatory CD4+ T cells may also have a role in the pathogenesis of mycoplasma respiratory diseases. We hypothesized Treg cells control the severity of the inflammatory lesions and may also promote persistence of infection. To examine this, BALB/c mice were depleted of CD25+ cells, and had increased disease severity due to Mycoplasma pulmonis infection. Increases in mycoplasma antibody responses and lymphocyte infiltration into lungs also occurred after CD25+ cell depletion. CD4+CD25+ regulatory T cells promoted IFN-? and IL-17 mycoplasma-specific CD4+ T cell responses in vitro and in vivo, while dampening IL-13+ Th responses. Neither IL-10 and TGF-? expression was detected in CD4+CD25+ T cells from lymph nodes. Thus, a regulatory T cell population plays an important role in controlling damaging immune responses in mycoplasma respiratory disease but does not contribute to persistence of infection. It appears that a regulatory T cell population preferentially dampens Th2 cell-mediated inflammatory responses to mycoplasma through a mechanism independent of IL-10 or TGF-? characteristic of "classic" Treg cells.
支原体(Mycoplasma)可引发以持续性感染和慢性气道炎症为特征的呼吸道疾病。支原体肺病属于免疫病理性疾病,CD4+辅助性T细胞(CD4+ T helper cells, Th)既可决定疾病严重程度,也可调控机体抗感染能力。其中,Th2细胞应答会加重免疫病理损伤,而Th1细胞则可赋予机体抗感染能力。不过,调节性CD4+ T细胞(regulatory CD4+ T cells, Treg)也可能参与支原体呼吸道疾病的发病过程。本研究提出假说:调节性T细胞可控制炎性损伤的严重程度,亦可能促进感染的持续。为验证该假说,研究人员对BALB/c小鼠实施CD25+细胞清除处理,结果显示肺支原体(Mycoplasma pulmonis)感染后的小鼠疾病严重程度升高。同时,CD25+细胞清除后还出现了支原体抗体应答增强以及淋巴细胞肺内浸润加剧的现象。体内外实验均证实,CD4+CD25+调节性T细胞(CD4+CD25+ regulatory T cells, Treg)可促进IFN-γ和IL-17阳性的支原体特异性CD4+ T细胞应答,同时抑制IL-13阳性的Th细胞应答。对淋巴结来源的CD4+CD25+ T细胞进行检测,未发现IL-10与转化生长因子-β(transforming growth factor-β, TGF-β)的表达。综上,调节性T细胞群在控制支原体呼吸道疾病中的破坏性免疫应答方面发挥重要作用,但并未促进感染的持续。现有研究表明,存在一类调节性T细胞可优先抑制针对支原体的Th2细胞介导的炎性应答,其通过不依赖IL-10或TGF-β的机制发挥作用,且该机制符合"经典"调节性T细胞的典型特征。



