小柯机器人

美国洛克菲勒大学Jean-Laurent Casanova、Rui Yang等研究人员合作发现，人类T-bet调控针对分枝杆菌的先天和类似先天的适应性IFN-γ免疫。该研究于2020年12月8日在线发表于国际一流学术期刊《细胞》。

研究人员报道了由于转录因子T-bet的遗传缺陷而导致分枝杆菌病的患者。该患者的循环分枝杆菌反应性自然杀伤（NK）、恒定NKT（iNKT）、粘膜相关恒定T（MAIT）和Vδ2⁺γδT淋巴细胞以及分枝杆菌的非响应性经典T_H1淋巴细胞的计数极低，这些细胞的残留群体也会产生异常少量的干扰素γ（IFN-γ）。其他淋巴细胞亚群正常发育，但产生低水平的IFN-γ，而CD8⁺αβT和非经典CD4⁺αβT_H1 *淋巴细胞除外，它们对分枝杆菌抗原产生正常反应（能够产生IFN-γ）。

因此，人类T-bet缺失通过阻止先天性（NK）和先天性适应性淋巴细胞（iNKT、MAIT和Vδ2⁺γδT细胞）的发育以及它们与分枝杆菌特异性IFN-γ产生而成为分枝杆菌疾病的基础，而且产生IFN-γ的纯适应性CD8⁺αβT和CD4⁺αβT_H1 *细胞无法弥补这一缺陷。

据悉，人IFN-γ免疫的先天性错误是分枝杆菌疾病的基础。

附：英文原文

Title: Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria

Author: Rui Yang, Federico Mele, Lisa Worley, David Langlais, Jérémie Rosain, Ibithal Benhsaien, Houda Elarabi, Carys A. Croft, Jean-Marc Doisne, Peng Zhang, Marc Weisshaar, David Jarrossay, Daniela Latorre, Yichao Shen, Jing Han, Masato Ogishi, Conor Gruber, Janet Markle, Fatima Al Ali, Mahbuba Rahman, Taushif Khan, Yoann Seeleuthner, Gaspard Kerner, Lucas T. Husquin, Julia L. Maclsaac, Mohamed Jeljeli, Abderrahmane Errami, Fatima Ailal, Michael S. Kobor, Carmen Oleaga-Quintas, Manon Roynard, Mathieu Bourgey, Jamila El Baghdadi, Stéphanie Boisson-Dupuis, Anne Puel, Fréderic Batteux, Flore Rozenberg, Nico Marr, Qiang Pan-Hammarstrm, Dusan Bogunovic, Lluis Quintana-Murci, Thomas Carroll, Cindy S. Ma, Laurent Abel, Aziz Bousfiha, James P. Di Santo, Laurie H. Glimcher, Philippe Gros

Issue&Volume: 2020-12-08

Abstract: Inborn errors of human interferon gamma (IFN-γ) immunity underlie mycobacterial disease.We report a patient with mycobacterial disease due to inherited deficiency of thetranscription factor T-bet. The patient has extremely low counts of circulating Mycobacterium-reactive natural killer (NK), invariant NKT (iNKT), mucosal-associated invariantT (MAIT), and Vδ2+ γδ T lymphocytes, and of Mycobacterium-non reactive classic TH1 lymphocytes, with the residual populations of these cells also producing abnormallysmall amounts of IFN-γ. Other lymphocyte subsets develop normally but produce lowlevels of IFN-γ, with the exception of CD8+ αβ T and non-classic CD4+ αβ TH1 lymphocytes, which produce IFN-γ normally in response to mycobacterial antigens.Human T-bet deficiency thus underlies mycobacterial disease by preventing the developmentof innate (NK) and innate-like adaptive lymphocytes (iNKT, MAIT, and Vδ2+ γδ T cells) and IFN-γ production by them, with mycobacterium-specific, IFN-γ-producing,purely adaptive CD8+ αβ T, and CD4+ αβ TH1 cells unable to compensate for this deficit.

DOI: 10.1016/j.cell.2020.10.046

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31453-7