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Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
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Mucosal-associated invariant T cell-rich congenic mouse strain allows functional evaluation
The Journal of Clinical Investigation
|November 3, 2015
Summary
Researchers identified a genetic trait in CAST/EiJ mice that significantly increases mucosal-associated invariant T cells (MAITs). This discovery enables better study of MAITs
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Mucosal-associated invariant T cells (MAITs) are crucial for antimicrobial defense but are rare in common laboratory mice, hindering research.
- The evolutionary conservation of MAITs suggests significant biological importance, yet their scarcity in mouse models limits in vivo studies.
Purpose of the Study:
- To identify genetic factors influencing MAIT cell frequency in mice.
- To develop and characterize a mouse model with increased MAIT cell numbers for studying MAIT biology and function.
- To investigate the phenotype, function, and disease relevance of MAITs in a suitable mouse model.
Main Methods:
- Comparative analysis of MAIT cell frequencies in CAST/EiJ and C57BL/6J mice.
- Genetic mapping to identify the locus responsible for increased MAITs.
- Generation of a MAIThi congenic strain and crossing with a Rorcgt-GFP reporter strain.
- Phenotypic and functional characterization of MAITs using flow cytometry, cytokine analysis, and in vivo infection models.
Main Results:
- MAIT cells were found to be 20 times more frequent in CAST/EiJ mice compared to C57BL/6J mice.
- A genetic trait linked to the TCR-α locus in CAST/EiJ mice was associated with higher MAIT cell frequency.
- The developed MAIThi congenic strain exhibited memory MAIT cells (CD44+) with tissue-homing properties (CCR6+CCR7-), expressing key transcription factors (PLZF, RORγt) and cytokine receptors (IL-7R, IL-18Rα, IL-12Rβ).
- Mouse MAITs demonstrated MR1-dependent recognition of bacterial compounds, produced Th1/2/17 cytokines, and reduced bacterial load during urinary tract infection.
Conclusions:
- A novel MAIThi congenic mouse strain has been generated, allowing for the study of naturally occurring MAIT cells.
- This model recapitulates key features of human MAIT cells, including phenotype and function.
- The MAIThi congenic strain provides a valuable tool for investigating MAIT cell roles in immunity and disease.

