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与慢性气道炎症为特征的呼吸道疾病。支原体肺炎属于免疫病理性疾病,CD4阳性辅助T细胞(CD4+ Th cells)同时决定疾病严重程度与抗感染能力。Th2细胞应答可促进免疫病理损伤,而Th1细胞则赋予机体抗感染能力。不过,调节性CD4阳性T细胞(regulatory CD4+ T cells)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(Treg cells)可调控炎性损伤的严重程度,亦可能促进感染持续。为验证该假说,研究人员对BALB/c小鼠实施CD25阳性细胞清除处理,结果显示小鼠感染肺炎支原体(Mycoplasma pulmonis)后疾病严重程度升高。经CD25阳性细胞清除处理后,小鼠的支原体抗体应答水平及肺内淋巴细胞浸润程度均有所上升。体内外实验均证实,CD4+CD25+调节性T细胞可促进干扰素-γ(IFN-γ)与白细胞介素-17(IL-17)相关的支原体特异性CD4阳性T细胞应答,同时抑制IL-13阳性Th细胞应答。从淋巴结分离的CD4+CD25+ T细胞中未检测到白细胞介素-10(IL-10)与转化生长因子-β(TGF-β)的表达。综上,一类调节性T细胞群在抑制支原体呼吸道疾病中的病理性免疫应答方面发挥重要作用,但并未促进感染持续。研究表明,该类调节性T细胞可通过不依赖“经典”调节性T细胞(classic Treg cells)特征性IL-10或TGF-β的机制,优先抑制Th2细胞介导的支原体炎性应答。
创建时间:
2016-05-26



