MAIT cells’ <em>in vivo</em> activation requirements — ASN Events

MAIT cells’ in vivo activation requirements (#83)

Huimeng Wang 1 , Lars Kjer-Nielsen 1 , Criselle D’Souza 1 , Timothy SC Hinks 1 , Lyudmila Kostenko 1 , XinYi Lim 1 , Sidonia BG Eckle 1 , Bronwyn S Meehan 1 , David C Jackson 1 , Ligong Liu 2 , Michele Teng 2 , Vijay K Kuchroo 3 , Di Yu 4 , Barbara Fazekas 5 , David P Fairlie 2 , James McCluskey 1 , Richard A Strugnell 1 , Alexandra J Corbett 1 , Zhenjun Chen 1
  1. Peter Doherty Institute,University of Melbourne, Melbourne, VIC, Australia
  2. Institute for Molecular Bioscience, The University of Queensland, Brisban, Queensland, Australia
  3. Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, The United States
  4. Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia
  5. Sydney Medical School, The university of Sydney, Sydney, NSW, Australia

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.