Mucosal-associated invariant T cell-rich congenie mouse strain allows functional evaluation

Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%-10% in blood). Despite strong evolutionary conservation of the invariant TCR-α chain and restricting molecule MR1, this population is rare in laboratory mouse strains (≅ 0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-α locus and led to higher usage of the distal Vα segments, including Vα19. We generated a [MAIT.sup.hi] congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory ([CD44.sup.+]) [CD4.sup.-][CD8.sup.lo/neg] T cells with tissue-homing properties ([CCR6.sup.+][CCR7.sup.-]). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18Rα, and IL-12Rβ and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptor γ (RORγt). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the [MAIT.sup.hi] congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease.
Introduction Mucosal-associated invariant T cells (MAITs) express an invariant TCR-α (iTCR-α) chain (iVα7.2-Jα33 in human and iVα19-Jα33 in mouse) restricted by the major histocompatibility complex (MHC) class I-related protein 1 [...]