Inflammatory Cytokine Production is Elevated in MAIT Cells Following Acute Exercise

Abstract

Mucosal associated invariant T (MAIT) cells occupy a unique niche within human immunity yet little is known regarding the effects of exercise on activation or cytokine production. PURPOSE: To determine if exercise alters MAIT cell proinflammatory cytokine production and early activation markers after submaximal aerobic exercise. METHODS: 17 healthy young males [age 22 (4y), VO2max 51.6 (10.2 mL/kg/min), %fat 18.0 (5.0%)] performed a graded exercise test on a cycle ergometer until volitional exhaustion. Participants cycled for 40 min at 86% of ventilatory threshold following an overnight fast. Peripheral blood mononuclear cells were isolated from blood samples obtained at rest, 0h and 1h after submaximal exercise. Following a 4h stimulation with phorbol 12-myristate 13-acetate and ionomycin, MAIT cells counts and intracellular interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα) and interleukin 17 (IL-17) production were quantified using flow cytometry. Data were analyzed using one-way ANOVA and are expressed as mean (SD). RESULTS: Stimulated Vα7.2+CD161+ MAIT cells were 2.3 (1.2%) of all T cells at rest and increased to 3.2 (2.2%) at 0h but this did not reach significance (p=0.134). MAIT cells expression of CD69 was 76.0 (13.4%) and remained constant with exercise. TNFα expression significantly increased with exercise before returning to baseline [rest: 71(18%), 0h: 79 (13%), 1h: 65 (19%); p=0.017] whereas IL-17 and IFNγ were unchanged. The total number of circulating cells significantly increased at 0h for MAIT cells [73.4 (85.6%); p=0.003] and MAIT cells expressing TNFα [89.4 (139.9%); p=0.018], IL-17 [275.4 (370.5%); p=0.026], but not IFNγ [64.5 (127.5%); p=0.061] with all counts returning to baseline at 1h. CONCLUSIONS: Submaximal aerobic exercise transiently increased the percentage and total number of MAIT cells expressing TNFα, which may aid in activation and recruitment of additional immune cells. The total number of MAIT cells positive for IL-17 and IFNγ are higher but are driven by the exercise-stimulated lymphocytosis. The increase in proinflammatory cytokine production is part of the enhanced immune response seen immediately following vigorous exercise and suggests that MAIT cells may play an important role within this response.