Expansion of MAIT cells in the combined absence of NKT and γδ-T cells

Authors:

• Xu, Calvin
• Li, Shihan
• Fulford, Thomas S
• Christo, Susan N
• Mackay, Laura K
• Gray, Daniel HD
• Uldrich, Adam P
• Pellicci, Daniel G
• I Godfrey, Dale
• Koay, Hui-Fern

Details:

Mucosal Immunology, Volume 16, Issue 4, 2023-08-31

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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.