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19i Mucosal-Associated Invariant T Cells Are Innate T Cells in the Gut Lamina Propria That Provide a Rapid and Diverse Cytokine Response1
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
Mucosal-associated invariant T (MAIT) cells reside primarily in the gut lamina propria and require commensal flora for selection/expansion. They are restricted by the highly conserved MHC class I-related molecule MR1 and, like most NK T cells, express an invariant TCR
chain. Although they probably contribute to gut immunity, MAIT cells have not been functionally characterized because they are so rare. To create a model in which they are more abundant, we generated transgenic mice expressing only the TCR chain (V19i) that defines MAIT cells. By directly comparing V19i transgenic mice on MR1+/+ and MR1–/– backgrounds, we were able to distinguish and characterize a population of V19i T cells dependent on MR1 for development. MR1-restricted V19i transgenic T cells recapitulate what is known about MAIT cell development. Furthermore, a relatively high proportion of transgenic MAIT cells express NK1.1, and most have a cell surface phenotype similar to that of V14i NK T cells. Finally, MR1-restricted V19i T cells secrete IFN-
, IL-4, IL-5, and IL-10 following TCR ligation, and we provide evidence for what may be two functionally distinct MAIT cell populations. These data strongly support the idea that MAIT cells contribute to the innate immune response in the gut mucosa.
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