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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >The self-antigen, thyroglobulin, induces antigen-experienced CD4~+ T cells from healthy donors to proliferate and promote production of the regulatory cytokine, interleukin-10, by monocytes
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The self-antigen, thyroglobulin, induces antigen-experienced CD4~+ T cells from healthy donors to proliferate and promote production of the regulatory cytokine, interleukin-10, by monocytes

机译：自身抗原甲状腺球蛋白可诱导来自健康供体的抗原经历过的CD4〜+ T细胞增殖并促进单核细胞产生调节性细胞因子白细胞介素10。

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Summary:Thyroglobulin (TG), as autoantigen, induces in vitro proliferation of T and B cells from normal individuals, but the cytokine production differs from that in patients with autoimmune thyroid disease. Here, we investigate whether normal T cells responding to TG are naive, or have previously encountered' TG in vivo, using their responses to classic primary and secondary antigens, keyhole limpet haemocyanin (KLH) and tetanus toxoid (TT), respectively, for comparison. While TG elicited T-cell proliferation kinetics typical of a secondary response, the cytokine profile was distinct from that for TT. Whereas TT induced pro-inflammatory cytokines [interleukin-2 (IL-2)/interferon-gamma (IFN-gamma)/IL-4/IL-5], TG evoked persistent release of the regulatory IL-10. Some donors, however, also responded with late IFN-gamma production, suggesting that the regulation by IL-10 could be overridden. Although monocytes were prime producers of IL-10 in the early TG response, a few IL-10-secreting CD4~+ T cells, primarily with CD45RO~+ memory phenotype, were also detected. Furthermore, T-cell depletion from the mononuclear cell preparation abrogated monocyte IL-10 production. Our findings indicate active peripheral tolerance towards TG in the normal population, with aberrant balance between pro- and anti-inflammatory cytokine responses for some donors. This observation has implications for autoantigen recognition in general, and provides a basis for investigating the dichotomy between physiological and pathological modes of auto-recognition.
机译：摘要：甲状腺球蛋白（TG）作为自身抗原，可诱导正常个体的T细胞和B细胞在体外增殖，但细胞因子的产生与自身免疫性甲状腺疾病患者的细胞因子产生不同。在这里，我们调查正常T细胞对TG的反应是否是幼稚的，或者以前曾在体内遇到过TG，分别使用它们对经典一级和二级抗原，匙孔血蓝蛋白（KLH）和破伤风类毒素（TT）的反应进行比较。 TG引发了典型的继发性反应的T细胞增殖动力学，但细胞因子谱却与TT不同。 TT诱导促炎性细胞因子[白介素2（IL-2）/干扰素-γ（IFN-γ）/ IL-4 / IL-5]，而TG则引起调节性IL-10的持续释放。但是，一些捐赠者也对IFN-γ的后期产生做出反应，这表明IL-10的调控可能被忽略。尽管单核细胞在早期TG反应中是IL-10的主要产生者，但也检测到一些分泌IL-10的CD4〜+ T细胞，主要具有CD45RO〜+记忆表型。此外，来自单核细胞制备的T细胞耗竭消除了单核细胞IL-10的产生。我们的发现表明正常人群对TG的活动性外周耐受性良好，某些供体的促炎和抗炎细胞因子反应之间存在异常平衡。该观察结果通常对自身抗原识别具有影响，并为研究生理学和病理学自动识别模式之间的二分法提供了基础。

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