IL-10-producing T cells suppress immune responses in anergic tuberculosis patients
IL-10-producing T cells suppress immune responses in anergic tuberculosis patients
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DOI：
10.1172/jci9918
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发表时间：
2000-05-01
影响因子：
15.9
通讯作者：
Goldfeld, AE
中科院分区：
文献类型：
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作者：
Boussiotis, VA;Tsai, EY;Goldfeld, AE
结核分枝杆菌的致死率仍然是感染性生物中最高的，与宿主的免疫反应不足有关。结核病的控制和治疗需要有效的细胞免疫反应，而在活动性结核病感染期间，缺乏对分枝杆菌抗原的迟发性超敏反应(DTH)，被定义为无能，与不良的临床结果有关。为了研究与这种无能相关的生化事件，我们筛查了206例肺结核患者，并根据他们对结核菌素纯化蛋白衍生物(PPD)缺乏皮肤反应性来确定无能患者。在体外用PPD刺激T细胞可诱导PPD+患者产生IL-10、干扰素-γ和增殖，而来自无能患者的细胞产生IL-10但不产生干扰素-γ，并且对这种治疗没有反应。此外，在无能患者中，产生IL-10的T细胞是结构性存在的，T细胞受体(TCR)介导的刺激导致TCR Zeta的缺陷磷酸化和ZAP-70和MAPK的缺陷激活。这些结果表明，在完整的人体宿主中，抗原可以在体内诱导T细胞无能，这为研究结核分枝杆菌逃避免疫监视的机制提供了新的见解。
The lethality of Mycobacterium tuberculosis remains the highest among infectious organisms and is linked to inadequate immune response of the host. Containment and cure of tuberculosis requires an effective cell-mediated immune response, and the absence, during active tuberculosis infection, of delayed-type hypersensitivity (DTH) responses to mycobacterial antigens, defined as anergy, is associated with poor clinical outcome. To investigate the biochemical events associated with this anergy, we screened 206 patients with pulmonary tuberculosis and identified anergic patients by their lack of dermal reactivity to tuberculin purified protein derivative (PPD). In vitro stimulation of T cells with PPD induced production of IL-10, IFN-gamma, and proliferation in PPD+ patients, whereas cells from anergic patients produced IL-10 but not IFN-gamma and failed to proliferate in response to this treatment. Moreover, in anergic patients IL-10-producing T cells were constitutively present, and T-cell receptor-mediated (TCR-mediated) stimulation resulted in defective phosphorylation of TCR zeta and defective activation of ZAP-70 and MAPK. These results show that T-cell anergy can be induced by antigen in vivo in the intact human host and provide new insights into mechanisms by which M, tuberculosis escapes immune surveillance.