Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
Infect Immun. 2012 Sep;80(9):3256-67. doi: 10.1128/IAI.00279-12. Epub 2012 Jul 9.
Mucosa-associated invariant T (MAIT) cells are a unique population of αβ T cells in mammals that reside preferentially in mucosal tissues and express an invariant Vα paired with limited Vβ T-cell receptor (TCR) chains. Furthermore, MAIT cell development is dependent upon the expression of the evolutionarily conserved major histocompatibility complex (MHC) class Ib molecule MR1. Using in vitro assays, recent studies have shown that mouse and human MAIT cells are activated by antigen-presenting cells (APCs) infected with diverse microbes, including numerous bacterial strains and yeasts, but not viral pathogens. However, whether MAIT cells play an important, and perhaps unique, role in controlling microbial infection has remained unclear. To probe MAIT cell function, we show here that purified polyclonal MAIT cells potently inhibit intracellular bacterial growth of Mycobacterium bovis BCG in macrophages (MΦ) in coculture assays, and this inhibitory activity was dependent upon MAIT cell selection by MR1, secretion of gamma interferon (IFN-γ), and an innate interleukin 12 (IL-12) signal from infected MΦ. Surprisingly, however, the cognate recognition of MR1 by MAIT cells on the infected MΦ was found to play only a minor role in MAIT cell effector function. We also report that MAIT cell-deficient mice had higher bacterial loads at early times after infection compared to wild-type (WT) mice, demonstrating that MAIT cells play a unique role among innate lymphocytes in protective immunity against bacterial infection.
黏膜相关恒定 T（MAIT）细胞是哺乳动物中一类独特的αβ T 细胞亚群，它们优先定位于黏膜组织，并表达不变的 Vα 与有限的 Vβ T 细胞受体（TCR）链。此外，MAIT 细胞的发育依赖于进化上保守的主要组织相容性复合体（MHC）类 Ib 分子 MR1 的表达。利用体外检测方法，最近的研究表明，鼠和人 MAIT 细胞可被多种微生物感染的抗原呈递细胞（APC）激活，包括许多细菌株和酵母，但不能被病毒病原体激活。然而，MAIT 细胞在控制微生物感染方面是否发挥重要作用，甚至是否具有独特作用，仍不清楚。为了研究 MAIT 细胞的功能，我们在此表明，在共培养实验中，纯化的多克隆 MAIT 细胞可强烈抑制巨噬细胞（MΦ）内牛分枝杆菌 BCG 的胞内细菌生长，这种抑制活性依赖于 MAIT 细胞被 MR1 选择、γ干扰素（IFN-γ）的分泌以及受感染的 MΦ 中先天的白细胞介素 12（IL-12）信号。然而，令人惊讶的是，MAIT 细胞对受感染 MΦ 上的 MR1 的同源识别，仅在 MAIT 细胞效应功能中起次要作用。我们还报告，与野生型（WT）小鼠相比，MAIT 细胞缺陷小鼠在感染早期的细菌负荷更高，这表明 MAIT 细胞在针对细菌感染的固有淋巴细胞保护性免疫中发挥独特作用。
