MAIT cells’ in vivo activation requirements (#83)
Mucosal associated invariant T (MAIT) cells detect the class I-like molecule MR1 complexed with conserved microbial riboflavin metabolites leading to subsequent MAIT cell activation and antibacterial host defence. The nature of the antigen presenting cells that activate MAIT cells and the factors that dictate their ultimate effector function are still not clear, therefore we established mouse models of different bacterial infections to evaluate these determinants. We observed that both classical haemopoietic APCs and non-bone marrow-derived APC could present antigens to MAIT cells and activate them efficiently, but the dominant APC was pathogen-dependent. In shaping effector function, the cytokines IL-12 and IL-23 both played key roles such that IL-12 tended to skew MAIT cells towards a Th1 profile whereas IL-23 directed MAIT cell effector function towards a Th17 profile simultaneously promoting MAIT cell proliferation. In addition, we found that the co-stimulating receptor, ICOS was critical for optimal MAIT cell activation. Our findings suggest how MAIT cell function might be modulated for therapeutic interventions.