Double positive thymocytes select mucosal-associated invariant T cells

N Seach, L Guerri, L Le Bourhis, Y Mburu… - The Journal of …, 2013 - journals.aai.org
N Seach, L Guerri, L Le Bourhis, Y Mburu, Y Cui, S Bessoles, C Soudais, O Lantz
The Journal of Immunology, 2013journals.aai.org
NKT and mucosal-associated invariant T (MAIT) cells express semi-invariant TCR and
restriction by nonclassical MHC class Ib molecules. Despite common features, the
respective development of NKT and MAIT subsets is distinct. NKTs proliferate extensively
and acquire effector properties prior to thymic export. MAIT cells exit the thymus as naive
cells and acquire an effector/memory phenotype in a process requiring both commensal
flora and B cells. During thymic development, NKTs are selected by CD1d-expressing …
Abstract
NKT and mucosal-associated invariant T (MAIT) cells express semi-invariant TCR and restriction by nonclassical MHC class Ib molecules. Despite common features, the respective development of NKT and MAIT subsets is distinct. NKTs proliferate extensively and acquire effector properties prior to thymic export. MAIT cells exit the thymus as naive cells and acquire an effector/memory phenotype in a process requiring both commensal flora and B cells. During thymic development, NKTs are selected by CD1d-expressing cortical thymocytes; however, the hematopoietic cell type responsible for MAIT cell selection remains unresolved. Using reaggregated thymic organ culture and bone marrow chimeras, we demonstrate that positive selection of mouse iVα19 transgenic and Vβ6 transgenic MAIT cell progenitors requires MHC-related 1–expressing CD4+ CD8+ double positive thymocytes, whereas thymic B cells, macrophages, and dendritic cell subsets are dispensable. Preincubation of double positive thymocytes with exogenous bacterial ligand increases MHC-related 1 surface expression and enhances mature MAIT cell activation in the in vitro cocultures. The revelation of a common cell type for the selection of both NKT and MAIT subsets raises questions about the mechanisms underlying acquisition of their specific features.
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