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Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation
- Source :
- Journal of Clinical Investigation, Journal of Clinical Investigation, 2015, 125 (11), pp.4171-4185. ⟨10.1172/JCI82424⟩, www.jci.org, Journal of Clinical Investigation, American Society for Clinical Investigation, 2015, 125 (11), pp.4171-4185. ⟨10.1172/JCI82424⟩, Journal of Clinical Investigation 11 (125), 4171-4185. (2015)
- Publication Year :
- 2015
- Publisher :
- HAL CCSD, 2015.
-
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-alpha chain and restricting molecule MR1, this population is rare in laboratory mouse strains (approximate to 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-alpha locus and led to higher usage of the distal V alpha segments, including V alpha 19. We generated a MAIT(hl) 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(-)CD8(lo/neg) T cells with tissue-homing properties (CCR6*CCR7(-)). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18R alpha, and IL-12R beta and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptory gamma (R0R gamma t). 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(hi) congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease.
- Subjects :
- MESH: Minor Histocompatibility Antigens
MESH: Nuclear Receptor Subfamily 1, Group F, Member 3
Receptors, Antigen, T-Cell, alpha-beta
MESH: Chemotaxis, Leukocyte
MESH: Urinary Tract Infections
Lymphocyte Activation
MESH: Mice, Knockout
MESH: Histocompatibility Antigens Class I
MESH: Promyelocytic Leukemia Zinc Finger Protein
Mice
0302 clinical medicine
Promyelocytic Leukemia Zinc Finger Protein
MESH: Animals
Mice, Knockout
0303 health sciences
education.field_of_study
Lymphokines
MESH: Receptors, Antigen, T-Cell, alpha-beta
Microbiota
MESH: Polymorphism, Single Nucleotide
General Medicine
Nuclear Receptor Subfamily 1, Group F, Member 3
Natural killer T cell
MESH: Crosses, Genetic
Chemotaxis, Leukocyte
medicine.anatomical_structure
Phenotype
Radiation Chimera
Urinary Tract Infections
MESH: Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
MESH: Immunologic Memory
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
MESH: Kruppel-Like Transcription Factors
Research Article
MESH: Lymphocyte Count
[SDV.IMM] Life Sciences [q-bio]/Immunology
Lymphoid Tissue
MESH: Radiation Chimera
MESH: Mice, Transgenic
T cell
Population
Congenic
Kruppel-Like Transcription Factors
Mice, Transgenic
Mucosal associated invariant T cell
Biology
MESH: Phenotype
Polymorphism, Single Nucleotide
Minor Histocompatibility Antigens
03 medical and health sciences
Mice, Congenic
MESH: Mice, Congenic
MESH: Mice, Inbred C57BL
MESH: Germ-Free Life
medicine
Animals
Germ-Free Life
Humans
MESH: Microbiota
Lymphocyte Count
Receptors, Cytokine
education
MESH: Lymphocyte Activation
MESH: Mice
Crosses, Genetic
030304 developmental biology
MESH: Humans
MESH: Lymphokines
T-cell receptor
Histocompatibility Antigens Class I
Laboratory mouse
Gene rearrangement
Molecular biology
MESH: Receptors, Cytokine
Mice, Inbred C57BL
Disease Models, Animal
MESH: Natural Killer T-Cells
MESH: Lymphoid Tissue
Natural Killer T-Cells
MESH: Disease Models, Animal
Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
Immunologic Memory
MESH: Female
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation, Journal of Clinical Investigation, 2015, 125 (11), pp.4171-4185. ⟨10.1172/JCI82424⟩, www.jci.org, Journal of Clinical Investigation, American Society for Clinical Investigation, 2015, 125 (11), pp.4171-4185. ⟨10.1172/JCI82424⟩, Journal of Clinical Investigation 11 (125), 4171-4185. (2015)
- Accession number :
- edsair.doi.dedup.....644f41ebbc4f1764869f11e52b9386a8