Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Australia.
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia.
Mucosal Immunol. 2023 Aug;16(4):446-461. doi: 10.1016/j.mucimm.2023.05.003. Epub 2023 May 13.
Mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, and γδT cells are collectively referred to as 'unconventional T cells' due to their recognition of non-peptide antigens and restriction to MHC-I-like molecules. However, the factors controlling their widely variable frequencies between individuals and organs are poorly understood. We demonstrated that MAIT cells are increased in NKT or γδT cell-deficient mice and highly expand in mice lacking both cell types. TCRα repertoire analysis of γδT cell-deficient thymocytes revealed altered Trav segment usage relative to wild-type thymocytes, highlighting retention of the Tcra-Tcrd locus from the 129 mouse strain used to generate Tcrd mice. This resulted in a moderate increase in distal Trav segment usage, including Trav1, potentially contributing to increased generation of Trav1-Traj33 MAIT cells in the Tcrd thymus. Importantly, adoptively transferred MAIT cells underwent increased homeostatic proliferation within NKT/gdT cell-deficient tissues, with MAIT cell subsets exhibiting tissue-specific homing patterns. Our data reveal a shared niche for unconventional T cells, where competition for common factors may be exploited to collectively modulate these cells in the immune response. Lastly, our findings emphasise careful assessment of studies using NKT or γδT cell-deficient mice when investigating the role of unconventional T cells in disease.
黏膜相关恒定 T（MAIT）细胞、自然杀伤 T（NKT）细胞和γδT 细胞由于其识别非肽抗原和 MHC-I 样分子的限制，被统称为“非常规 T 细胞”。然而，控制它们在个体和器官之间广泛变化频率的因素知之甚少。我们证明，MAIT 细胞在 NKT 或 γδT 细胞缺陷小鼠中增加，并在缺乏这两种细胞类型的小鼠中高度扩增。γδT 细胞缺陷型胸腺细胞的 TCRα 库分析显示，与野生型胸腺细胞相比，Trav 节段的使用发生了改变，突出了从用于产生 Tcrd 小鼠的 129 小鼠品系保留的 Tcra-Tcrd 基因座。这导致远端 Trav 节段的使用适度增加，包括 Trav1，可能有助于增加 Tcrd 胸腺中的 Trav1-Traj33 MAIT 细胞的生成。重要的是，在 NKT/gdT 细胞缺陷组织中，经体外转移的 MAIT 细胞经历了更高的稳态增殖，MAIT 细胞亚群表现出组织特异性归巢模式。我们的数据揭示了非常规 T 细胞的共享生态位，其中对共同因子的竞争可能被用来集体调节这些细胞在免疫反应中的作用。最后，我们的研究结果强调，在研究非常规 T 细胞在疾病中的作用时，需要仔细评估使用 NKT 或 γδT 细胞缺陷小鼠的研究。
