Human MAIT cells are devoid of alloreactive potential: prompting their use as universal cells for adoptive immune therapy

BACKGROUND: Mucosal-associated invariant T (MAIT) cells are semi-invariant T cells that recognize microbial antigens presented by the highly conserved MR1 molecule. MAIT cells are predominantly localized in the liver and barrier tissues and are potent effectors of antimicrobial defense. MAIT cells are very few at birth and accumulate gradually over a period of about 6 years during the infancy. The cytotoxic potential of MAIT cells, as well as their newly described regulatory and tissue repair functions, open the possibility of exploiting their properties in adoptive therapy. A prerequisite for their use as ‘universal’ cells would be a lack of alloreactive potential, which remains to be demonstrated. METHODS: We used ex vivo, in vitro and in vivo models to determine if human MAIT cells contribute to allogeneic responses. RESULTS: We show that recovery of MAIT cells after allogeneic hematopoietic stem cell transplantation recapitulates their slow physiological expansion in early childhood, independent of recovery of non-MAIT T cells. In vitro, signals provided by allogeneic cells and cytokines do not induce sustained MAIT cell proliferation. In vivo, human MAIT cells do not expand nor accumulate in tissues in a model of T-cell-mediated xenogeneic graft-versus-host disease in immunodeficient mice. CONCLUSIONS: Altogether, these results provide evidence that MAIT cells are devoid of alloreactive potential and pave the way for harnessing their translational potential in universal adoptive therapy overcoming barriers of HLA disparity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number NCT02403089.