Highlights d Human CD26 hi CD94 lo Vd2Vg9 T cells exhibit a MAIT cell-like phenotype d CD26 and CD94 regulate Vd2 cytokine responses and cytotoxicity d Cord blood Vd2Vg9 cells are predominately CD26 hi CD94 lo d Exposure of CD26 hi CD94 lo cells to antigen and IL-23 induces a cytotoxic phenotype

Methods Twenty healthy young males with moderate fitness levels performed an extended graded exercise test until volitional fatigue. Peripheral blood mononuclear cells were isolated from venous blood obtained prior and immediately after exercise and were labeled to identify specific T cell populations using flow cytometry. Results The percentage of MAIT cells relative to total T cells significantly increased from 3.0 to 3.8% and absolute MAIT cell counts increased by 2.2-fold following maximal exercise. MAIT cell subpopulation proportions were unchanged with exercise. Within cytotoxic T lymphocytes (CTL), MAIT cells consisted of 8% of these cells and this remained constant after exercise. MAIT cell counts and changes with exercise were not affected by body composition, VO 2peak , or exercise duration. Conclusions Maximal exercise doubled MAIT cell numbers and showed preferential mobilization within total T cells but the response was not influenced by fitness levels, exercise duration, or body composition. These results suggest that acute exercise could be used to offset MAIT cell deficiencies observed with certain pathologies. MAIT cells also make up a substantial proportion of CTLs, which may have implications for cytotoxicity assays using these cells. Keywords TCR Vα7.2 · Exercise immunology · MAIT cells

Significance Whereas T cells are known to recognize peptides, vitamin B metabolites, or lipid antigens, we identify several nonlipidic small molecules classified as pentamethylbenzofuransulfonates (PBFs) that activate a population of CD1d-restricted natural killer T (NKT) cells. This represents a breakthrough in the field of NKT cell biology. This study also reveals a previously unknown population of PBF-reactive NKT cells in healthy individuals with stereotyped receptors that paves the way for future studies of the role of these cells in immunity, including sulfa drug hypersensitivity.