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Development of MAIT cells in neonates and after hematopoietic stem cell transplantation
MAIT cells are invariant T lymphocytes that recognise vitamin B2 precursors synthesised by most bacteria. MAIT cells thus have a powerful antimicrobial function, particularly in mucosal tissues, where they are commonly located. Although they are scarce at birth, MAIT cells are plentiful by adulthood. NEOMAIT aimed to determine the physiological mechanisms causing this expansion. By monitoring cohorts of neonates, the project showed that the number of MAIT cells grows very gradually from birth to the age of six. The same kinetics were observed following hematopoietic stem cell transplantation. These results suggest that MAIT cell expansion arises from successive encounters between a few clones and appropriate microbial derivatives, rather than factors intrinsic to each individual.
ANR programme: AAPG CES15
Edition, project duration: 2014, 60 months
ANR grant: € 561,533
DGOS co-funding : € 284,054
- Sophie Caillat-Zucman
Project region: Île-de-France
Main publication or contribution:
- Ben Youssef G, Tourret M, Salou M, Ghazarian L, Houdouin H, Mondot S, Mburu Y, Lambert M, Azarnoush A, Diana JS, Virlouvet AL, Peuchmaur M, Schmitz T, Dalle JH, Lantz O, Biran V and Caillat-Zucman S. Ontogeny of human Mucosal-Associated Invariant T cells and related T cell subsets. J. Exp. Med. 2018, 215 (2) : 459-479. doi 10.1084/jem.20171739.
- F. Legoux, D. Bellet, C. Daviaud, Y.El Morr, A. Darbois, K. Niort, E. Procopio, M. Salou, J. Gilet, B. Ryffel, A. Balvay, A. Foussier, M. Sarkis, A. El Marjou, F. Schmidt, S. Rabot and O. Lantz.. Microbial metabolites control the thymic development of Mucosal Associated Invariant T cells. Science 2019 ; 366, 494-499.
- Institut Curie.
- APHP, cofinancement DGOS.
By showing that the physiological expansion of MAIT cells depends on microbial antigens, the results prepare the ground for the possible use of MAIT cells in adoptive allogeneic immunotherapy, and particularly the production of MAIT cells carrying a chimeric receptor (CAR-MAIT) as a treatment for tumours (patent EP18306743.8).