Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines

Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines
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DOI:
10.1002/eji.201445193
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发表时间:
2015-04-01
影响因子:
5.4
通讯作者:
Dieli,Francesco
Dieli,Francesco
中科院分区:
医学3区
文献类型:
--
作者:
Caccamo,Nadia;Pietra,Gabriella;Dieli,Francesco

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CD8 T细胞有助于抵抗结核分枝杆菌的保护性免疫。在人类中,M。结核反应性CD8 T细胞通常识别与经典MHC Ia类分子相关的肽,但关于CD8 T细胞识别m的信息很少。由非经典MHC类Ib分子呈现的结核菌ags。我们在此表明,来自结核病(TB)患者的CD8 T细胞识别HLA - E - bindingM。CD3/TCR αβ介导和CD8依赖的方式,代表了在免疫应答toM中起作用的另一种效应细胞。活动性感染期间的结核病。HLA‐E‐限制m的识别。结核菌肽可通过四聚体特异性循环CD8 T细胞在活动性结核病期间显著增强的离体频率检测到。这些CD8 T细胞在体外抗原刺激下产生2型细胞因子,帮助B细胞产生Ab,并介导有限的TRAIL依赖性细胞溶解和对dm的杀微生物活性。结核菌感染的靶细胞。我们的研究结果,连同HLA‐E/M。在合并或未合并HIV感染的结核病患者中检测到结核肽特异性CD8 T细胞,表明这是一种参与结核病免疫应答的新的人类T细胞群。
CD8 T cells contribute to protective immunity againstMycobacterium tuberculosis. In humans,M. tuberculosisreactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizingM. tuberculosisAgs presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA‐E‐bindingM. tuberculosispeptides in a CD3/TCR αβ mediated and CD8‐dependent manner, and represent an additional type of effector cells playing a role in immune response toM. tuberculosisduring active infection. HLA‐E‐restricted recognition ofM. tuberculosispeptides is detectable by a significant enhanced ex vivo frequency of tetramer‐specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL‐dependent cytolytic and microbicidal activity towardM. tuberculosisinfected target cells. Our results, together with the finding that HLA‐E/M. tuberculosispeptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T‐cell population that participates in immune response in TB.