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Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers.

Rahimpour A, Koay HF, Enders A, Clanchy R, Eckle SB, Meehan B, Chen Z, Whittle B, Liu L, Fairlie DP, Goodnow CC, McCluskey J, Rossjohn J, Uldrich AP, Pellicci DG, Godfrey DI - J. Exp. Med. (2015)

Bottom Line: These cells include CD4(-)CD8(-), CD4(-)CD8(+), and CD4(+)CD8(-) subsets, and their frequency varies in a tissue- and strain-specific manner.Mouse MAIT cells have a CD44(hi)CD62L(lo) memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-γ, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels.These observations contrast with previous reports that MAIT cells from Vα19 TCR transgenic mice are PLZF(-) and express a naive CD44(lo) phenotype.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.

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Most MAIT cells are RORγthi and produce IL-17A. (A) MAIT cells, NKT cells (CD1d–α-GalCer tetramer+), and conventional TCR-β+ T cells were labeled with antibodies specific for RORγt and T-bet. (B) Samples from thymus, spleen, and lung were stimulated for 4 h in vitro with PMA/ionomycin, and expression of RORγt and T-bet and production of IFN-γ and IL-17A by MAIT and NKT cells were analyzed by flow cytometry. Data are representative of four experiments, with a combined total of eight mice.
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fig6: Most MAIT cells are RORγthi and produce IL-17A. (A) MAIT cells, NKT cells (CD1d–α-GalCer tetramer+), and conventional TCR-β+ T cells were labeled with antibodies specific for RORγt and T-bet. (B) Samples from thymus, spleen, and lung were stimulated for 4 h in vitro with PMA/ionomycin, and expression of RORγt and T-bet and production of IFN-γ and IL-17A by MAIT and NKT cells were analyzed by flow cytometry. Data are representative of four experiments, with a combined total of eight mice.

Mentions: Given that MAIT cells express high levels of IL-17A and low levels of IFN-γ, we next examined the transcription factors RORγt and T-bet, which in other cell types including NKT cells are associated with production of these cytokines, respectively (Lee et al., 2013). These results showed that most MAIT cells expressed RORγt, whereas only a small subset (∼5–30%) expressed T-bet, and these transcription factors appeared to be mutually exclusive (Fig. 6 A). In contrast, most NKT cells expressed T-bet and only a small subset expressed RORγt, whereas conventional T cells mostly lacked these transcription factors (Fig. 6 A). To directly test whether these transcription factors are associated with the cytokine profile of mouse MAIT cells, we investigated cytokine production by RORγt+ and T-bet+ MAIT cells isolated from thymus. These data indicated that the rare IFN-γ+ MAIT cells were T-bet+RORγtlo, whereas IL-17A was exclusively produced by the RORγthi MAIT cells. Although some of the IL-17A+ MAIT cells also appeared to express low levels of T-bet (Fig. 6 B), we noted that T-bet expression moderately increased on MAIT cells upon stimulation (Fig. 6 B). Thus, it is likely that the IL-17A+RORγthi MAIT cells were derived from the predominant T-bet− MAIT cell population, whereas IFN-γ was produced by the T-bet+RORγtlo MAIT cells (Fig. 6 B). Collectively, these results suggested the existence of two functionally distinct populations of MAIT cells, governed by differential transcription factor expression in mice.


Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers.

Rahimpour A, Koay HF, Enders A, Clanchy R, Eckle SB, Meehan B, Chen Z, Whittle B, Liu L, Fairlie DP, Goodnow CC, McCluskey J, Rossjohn J, Uldrich AP, Pellicci DG, Godfrey DI - J. Exp. Med. (2015)

Most MAIT cells are RORγthi and produce IL-17A. (A) MAIT cells, NKT cells (CD1d–α-GalCer tetramer+), and conventional TCR-β+ T cells were labeled with antibodies specific for RORγt and T-bet. (B) Samples from thymus, spleen, and lung were stimulated for 4 h in vitro with PMA/ionomycin, and expression of RORγt and T-bet and production of IFN-γ and IL-17A by MAIT and NKT cells were analyzed by flow cytometry. Data are representative of four experiments, with a combined total of eight mice.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4493408&req=5

fig6: Most MAIT cells are RORγthi and produce IL-17A. (A) MAIT cells, NKT cells (CD1d–α-GalCer tetramer+), and conventional TCR-β+ T cells were labeled with antibodies specific for RORγt and T-bet. (B) Samples from thymus, spleen, and lung were stimulated for 4 h in vitro with PMA/ionomycin, and expression of RORγt and T-bet and production of IFN-γ and IL-17A by MAIT and NKT cells were analyzed by flow cytometry. Data are representative of four experiments, with a combined total of eight mice.
Mentions: Given that MAIT cells express high levels of IL-17A and low levels of IFN-γ, we next examined the transcription factors RORγt and T-bet, which in other cell types including NKT cells are associated with production of these cytokines, respectively (Lee et al., 2013). These results showed that most MAIT cells expressed RORγt, whereas only a small subset (∼5–30%) expressed T-bet, and these transcription factors appeared to be mutually exclusive (Fig. 6 A). In contrast, most NKT cells expressed T-bet and only a small subset expressed RORγt, whereas conventional T cells mostly lacked these transcription factors (Fig. 6 A). To directly test whether these transcription factors are associated with the cytokine profile of mouse MAIT cells, we investigated cytokine production by RORγt+ and T-bet+ MAIT cells isolated from thymus. These data indicated that the rare IFN-γ+ MAIT cells were T-bet+RORγtlo, whereas IL-17A was exclusively produced by the RORγthi MAIT cells. Although some of the IL-17A+ MAIT cells also appeared to express low levels of T-bet (Fig. 6 B), we noted that T-bet expression moderately increased on MAIT cells upon stimulation (Fig. 6 B). Thus, it is likely that the IL-17A+RORγthi MAIT cells were derived from the predominant T-bet− MAIT cell population, whereas IFN-γ was produced by the T-bet+RORγtlo MAIT cells (Fig. 6 B). Collectively, these results suggested the existence of two functionally distinct populations of MAIT cells, governed by differential transcription factor expression in mice.

Bottom Line: These cells include CD4(-)CD8(-), CD4(-)CD8(+), and CD4(+)CD8(-) subsets, and their frequency varies in a tissue- and strain-specific manner.Mouse MAIT cells have a CD44(hi)CD62L(lo) memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-γ, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels.These observations contrast with previous reports that MAIT cells from Vα19 TCR transgenic mice are PLZF(-) and express a naive CD44(lo) phenotype.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.

Show MeSH
Related in: MedlinePlus