MAIT cells expand in the absence of NKT and gdT cells

We showed that NKT cell-deficient mice have increased MAIT cells and demonstrated that this increase was due to the loss of NKT cells rather than their restricting element, CD1d. MAIT cells were also markedly increased in gdT cell-deficient mice and expand further in NKT/gdT cell double-deficient mice. Expanded MAIT cells phenotypically and functionally resembled their wildtype (WT) counterparts. As gdT-deficient mice harbor a modified TCRd locus, our findings imply that TCRa rearrangement may be altered in these mice, potentially manifesting in greater rearrangement of distal Trav gene segments like Trav1 and increased intrathymic generation of MAIT cells. However, increases in peripheral MAIT cells exceeded increases in the thymus, indicating that MAIT cells may compete with peripheral NKT and gdT cells for similar homeostatic factors and expand in their absence. Accordingly, we show that adoptively transferred MAIT cells underwent more proliferation within NKT/gdT-deficient hosts relative to WT controls. Together, our findings highlight a shared niche in which MAIT, NKT, and gdT cells co-exist and compete for common homeostatic factors. Importantly, these findings provide insights into factors regulating MAIT cell levels and cautions the interpretation of studies on NKT and gdT cells using NKT- or gdT-deficient mice, respectively, due to previously unappreciated increases in MAIT cell levels and potential alterations in TCRa chain rearrangement in gdT-deficient mice.