Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation
Yue Cui, Katarzyna Franciszkiewicz, Yvonne K. Mburu, Stanislas Mondot, Lionel Le Bourhis, Virginie Premel, Emmanuel Martin, Alexandra Kachaner, Livine Duban, Molly A. Ingersoll, Sylvie Rabot, Jean Jaubert, Jean-Pierre De Villartay, Claire Soudais, Olivier Lantz
Yue Cui, Katarzyna Franciszkiewicz, Yvonne K. Mburu, Stanislas Mondot, Lionel Le Bourhis, Virginie Premel, Emmanuel Martin, Alexandra Kachaner, Livine Duban, Molly A. Ingersoll, Sylvie Rabot, Jean Jaubert, Jean-Pierre De Villartay, Claire Soudais, Olivier Lantz
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Research Article Immunology

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

Abstract

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 MAIThi congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44+) CD4–CD8lo/neg T cells with tissue-homing properties (CCR6+CCR7–). 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 MAIThi congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease.

Authors

Yue Cui, Katarzyna Franciszkiewicz, Yvonne K. Mburu, Stanislas Mondot, Lionel Le Bourhis, Virginie Premel, Emmanuel Martin, Alexandra Kachaner, Livine Duban, Molly A. Ingersoll, Sylvie Rabot, Jean Jaubert, Jean-Pierre De Villartay, Claire Soudais, Olivier Lantz

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Figure 5

Phenotype and cytokine production by mouse MAITs.

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Phenotype and cytokine production by mouse MAITs. (A and B) Surface expr...
(A and B) Surface expression of the indicated markers was analyzed on Thy1.2+TCR-β+ T cells from the (A) spleen or (B) liver of Rorcgt-GFPTG B6-MAITCAST mice. The indicated subsets were studied: MAITs (DN/CD8loCD44+GFP+), memory CD8+ T cells (CD8hiCD44+), and NKT cells (CD1d-αGC-Tet+). Shaded histograms show isotype or FMO control (CD103). Representative of at least 3 experiments. (C) Expression of PLZF and RORγt-GFP by DN/CD8loCD1d-αGC-Tet– TCR-β+ T cells from Mr1+/+ or Mr1–/– Rorcgt-GFPTG B6-MAITCAST mice. (D) Cytokine secretion by MAITs in comparison with control populations. T cells from the spleen of Rorcgt-GFPTG B6-MAITCAST mice were identified as Thy1.2+TCR-β+ cells, and memory (CD44+) CD4+ or CD8+, MAIT (DN/CD8loCD44+GFP+), and NKT (CD1d-α-GC-Tet+) subsets were FACS sorted. Eight-thousand cells from each sorted T cell subset were cultured with anti-CD3/28 beads (1:1) for 42 to 45 hours and the cytokine content measured in the culture supernatant. The results were derived from 4 to 7 separate cultures collected over 3 independent experiments. Each dot represents an individual sort. Dashed line indicates quantitation limit. Dots on the x axis indicate not detected.