Mucosal-associated invariant T (MAIT) cells are activated in a TCR-dependent manner by antigens derived from the riboflavin synthesis pathway, including 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU), bound to MHC-related protein-1 (MR1). However, MAIT cell activation in vivo has not been studied in detail. Here, we have found and characterized additional molecular signals required for optimal activation and expansion of MAIT cells after pulmonary Legionella or Salmonella infection in mice. We show that either bone marrow–derived APCs or non–bone marrow–derived cells can activate MAIT cells in vivo, depending on the pathogen. Optimal MAIT cell activation in vivo requires signaling through the inducible T cell costimulator (ICOS), which is highly expressed on MAIT cells. Subsequent expansion and maintenance of MAIT-17/1-type responses are dependent on IL-23. Vaccination with IL-23 plus 5-OP-RU augments MAIT cell–mediated control of pulmonary Legionella infection. These findings reveal cellular and molecular targets for manipulating MAIT cell function under physiological conditions.

粘膜相关不变性T（MAIT）细胞以TCR依赖性方式被核黄素合成途径衍生的抗原激活，包括结合至（5-OP-RU）的5-（2-氧代丙叉基亚氨基）-6- d-核糖基氨基尿嘧啶（5-OP-RU）。 MHC相关蛋白1（MR1）。然而，尚未详细研究体内MAIT细胞活化。在这里，我们发现并表征了肺退伍军人病菌或沙门氏菌后MAIT细胞最佳活化和扩增所需的其他分子信号小鼠感染。我们证明，取决于病原体，骨髓来源的APC或非骨髓来源的细胞均可在体内激活MAIT细胞。体内最佳MAIT细胞活化需要通过可诱导T细胞共刺激物（ICOS）进行信号传导，该信号在MAIT细胞上高度表达。MAIT-17 / 1型反应的后续扩展和维持取决于IL-23。IL-23加5-OP-RU的疫苗接种增强了MAIT细胞介导的肺退伍军人杆菌感染控制。这些发现揭示了在生理条件下操纵MAIT细胞功能的细胞和分子靶标。