Moreira Marcela de Lima, Tsuji Moriya, Corbett Alexandra Jane, Araújo Márcio Sobreira Silva, Teixeira-Carvalho Andréa, Martins-Filho Olindo Assis, Peruhype-Magalhães Vanessa, Coelho-Dos-Reis Jordana Grazziela
Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA.
Immunol Lett. 2017 Jul;187:53-60. doi: 10.1016/j.imlet.2017.05.007. Epub 2017 May 16.
It has been almost two decades since the discovery of mucosal-associated invariant T (MAIT)-cells. Several advances in the field have been made such as the discovery of the antimicrobial activity of MAIT-cells, the abundance of these cells in human mucosa and in liver and the discovery of ligands able to bind MR1 and activate MAIT-cells. MAIT-cells are a unique subset of innate-like T-cells that express a canonical T-cell receptor with the alpha chain containing hAV7S2 and AJ33 in humans (TCRVα7.2Jα33) and respond to bacterial/fungus vitamin B2 metabolites by an MR1-dependent pathway. Indirect activation is also observed during chronic viral infections by and IL-12/IL-18 pathway. In this review, the mechanisms of activation, the timeline of MAIT-cell development in humans as well as their role in human infection are discussed. On the whole, we believe that harnessing the anti-microbial ability of MAIT-cells could contribute for the design of potent immunotherapies and vaccines against "hard-to-kill" infectious agents that remain as public health threats worldwide.
自黏膜相关恒定T(MAIT)细胞被发现以来,已经过去了近二十年。该领域取得了多项进展,例如发现了MAIT细胞的抗菌活性、这些细胞在人体黏膜和肝脏中的丰富程度以及能够结合MR1并激活MAIT细胞的配体。MAIT细胞是一类独特的固有样T细胞亚群,在人类中表达具有α链的典型T细胞受体,该α链包含hAV7S2和AJ33(TCRVα7.2Jα33),并通过MR1依赖性途径对细菌/真菌维生素B2代谢产物作出反应。在慢性病毒感染期间,还通过IL-12/IL-18途径观察到间接激活。在这篇综述中,我们讨论了MAIT细胞的激活机制、人类MAIT细胞发育的时间线以及它们在人类感染中的作用。总体而言我们认为,利用MAIT细胞的抗菌能力有助于设计针对“难以杀灭”的传染原的有效免疫疗法和疫苗,这些传染原仍然是全球公共卫生威胁。