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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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MAIT cells express PLZF and are PLZF dependent. (A) MAIT cells from WT B6 mice (top row) and Vα19 TCR Tg Cα−/− mice (bottom row). Plots in first column depict lymphocytes with B220+ B cells excluded by electronic gating. Numbers indicate the percentage of MAIT cells (red gate) of total αβ T cells (black gate). MAIT cells and non-MAIT “T cells,” gated as shown in the first column, were examined for PLZF versus TCR-β (second and third columns) and PLZF versus CD44 (fourth and fifth columns) expression. Data are representative of four separate experiments with a combined total of six mice per group. (B) Scatter plots depict the percentage of PLZF+ and CD44+ MAIT cells from spleen and lung of WT and Vα19 TCR transgenic Cα−/− mice. Each symbol represents an individual mouse. Bars depict mean ± SEM from a total of six separate mice. (C) Presence of MAIT cells in thymus, spleen, and lymph nodes of B6 WT and PLZF mice. Plots depict lymphocytes with B220+ B cells excluded by electronic gating. Top row shows PLZF mice, and bottom row shows WT mice. Numbers indicate the percentage of MAIT cells (red gate) of total αβ T cells (black gate). Data are representative of three independent experiments with a combined total of six to seven mice per group. (D) Percentage (top row) and total numbers (bottom row) of MAIT and NKT cells (CD1d–α-GalCer tetramer+ T cells) of total lymphocytes in thymus, spleen, and lymph nodes. Each symbol represents a different mouse. Bars depict mean ± SEM. For C and D, data are representative of three independent experiments with a combined total of six to seven mice per group. **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 using a Mann–Whitney rank sum U test.
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fig4: MAIT cells express PLZF and are PLZF dependent. (A) MAIT cells from WT B6 mice (top row) and Vα19 TCR Tg Cα−/− mice (bottom row). Plots in first column depict lymphocytes with B220+ B cells excluded by electronic gating. Numbers indicate the percentage of MAIT cells (red gate) of total αβ T cells (black gate). MAIT cells and non-MAIT “T cells,” gated as shown in the first column, were examined for PLZF versus TCR-β (second and third columns) and PLZF versus CD44 (fourth and fifth columns) expression. Data are representative of four separate experiments with a combined total of six mice per group. (B) Scatter plots depict the percentage of PLZF+ and CD44+ MAIT cells from spleen and lung of WT and Vα19 TCR transgenic Cα−/− mice. Each symbol represents an individual mouse. Bars depict mean ± SEM from a total of six separate mice. (C) Presence of MAIT cells in thymus, spleen, and lymph nodes of B6 WT and PLZF mice. Plots depict lymphocytes with B220+ B cells excluded by electronic gating. Top row shows PLZF mice, and bottom row shows WT mice. Numbers indicate the percentage of MAIT cells (red gate) of total αβ T cells (black gate). Data are representative of three independent experiments with a combined total of six to seven mice per group. (D) Percentage (top row) and total numbers (bottom row) of MAIT and NKT cells (CD1d–α-GalCer tetramer+ T cells) of total lymphocytes in thymus, spleen, and lymph nodes. Each symbol represents a different mouse. Bars depict mean ± SEM. For C and D, data are representative of three independent experiments with a combined total of six to seven mice per group. **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 using a Mann–Whitney rank sum U test.

Mentions: The transcription factor PLZF is considered to be a master regulator of innate-like T cells, including NKT cells (Kovalovsky et al., 2008; Savage et al., 2008) and γδ T cells (Kreslavsky et al., 2009). We examined PLZF expression in mouse MAIT cells from spleens of B6 WT and Vα19 TCR transgenic.Cα−/− mice (Fig. 4 A). Whereas the WT MAIT cells were almost all PLZFhi, most of the TCR transgenic MAIT cells from spleen were PLZFlo, which is reminiscent of a previous study suggesting that Vα19 TCR transgenic.Cα−/− MAIT cells lacked this transcription factor (Martin et al., 2009). Interestingly, the percentage of Vα19 TCR transgenic MAIT cells that were PLZFhi was higher in lung (mean 61%) compared with spleen (mean 33%; Fig. 4 B). Nearly all (>95%) of the PLZFhi MAIT cells also expressed high levels of the memory T cell marker CD44, regardless of whether they were from WT or Vα19 TCR transgenic mice, whereas many but not all of the PLZFlo MAIT cells that were abundant in the TCR transgenic mice also lacked CD44 expression (Fig. 4, A and B).


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)

MAIT cells express PLZF and are PLZF dependent. (A) MAIT cells from WT B6 mice (top row) and Vα19 TCR Tg Cα−/− mice (bottom row). Plots in first column depict lymphocytes with B220+ B cells excluded by electronic gating. Numbers indicate the percentage of MAIT cells (red gate) of total αβ T cells (black gate). MAIT cells and non-MAIT “T cells,” gated as shown in the first column, were examined for PLZF versus TCR-β (second and third columns) and PLZF versus CD44 (fourth and fifth columns) expression. Data are representative of four separate experiments with a combined total of six mice per group. (B) Scatter plots depict the percentage of PLZF+ and CD44+ MAIT cells from spleen and lung of WT and Vα19 TCR transgenic Cα−/− mice. Each symbol represents an individual mouse. Bars depict mean ± SEM from a total of six separate mice. (C) Presence of MAIT cells in thymus, spleen, and lymph nodes of B6 WT and PLZF mice. Plots depict lymphocytes with B220+ B cells excluded by electronic gating. Top row shows PLZF mice, and bottom row shows WT mice. Numbers indicate the percentage of MAIT cells (red gate) of total αβ T cells (black gate). Data are representative of three independent experiments with a combined total of six to seven mice per group. (D) Percentage (top row) and total numbers (bottom row) of MAIT and NKT cells (CD1d–α-GalCer tetramer+ T cells) of total lymphocytes in thymus, spleen, and lymph nodes. Each symbol represents a different mouse. Bars depict mean ± SEM. For C and D, data are representative of three independent experiments with a combined total of six to seven mice per group. **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 using a Mann–Whitney rank sum U test.
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fig4: MAIT cells express PLZF and are PLZF dependent. (A) MAIT cells from WT B6 mice (top row) and Vα19 TCR Tg Cα−/− mice (bottom row). Plots in first column depict lymphocytes with B220+ B cells excluded by electronic gating. Numbers indicate the percentage of MAIT cells (red gate) of total αβ T cells (black gate). MAIT cells and non-MAIT “T cells,” gated as shown in the first column, were examined for PLZF versus TCR-β (second and third columns) and PLZF versus CD44 (fourth and fifth columns) expression. Data are representative of four separate experiments with a combined total of six mice per group. (B) Scatter plots depict the percentage of PLZF+ and CD44+ MAIT cells from spleen and lung of WT and Vα19 TCR transgenic Cα−/− mice. Each symbol represents an individual mouse. Bars depict mean ± SEM from a total of six separate mice. (C) Presence of MAIT cells in thymus, spleen, and lymph nodes of B6 WT and PLZF mice. Plots depict lymphocytes with B220+ B cells excluded by electronic gating. Top row shows PLZF mice, and bottom row shows WT mice. Numbers indicate the percentage of MAIT cells (red gate) of total αβ T cells (black gate). Data are representative of three independent experiments with a combined total of six to seven mice per group. (D) Percentage (top row) and total numbers (bottom row) of MAIT and NKT cells (CD1d–α-GalCer tetramer+ T cells) of total lymphocytes in thymus, spleen, and lymph nodes. Each symbol represents a different mouse. Bars depict mean ± SEM. For C and D, data are representative of three independent experiments with a combined total of six to seven mice per group. **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 using a Mann–Whitney rank sum U test.
Mentions: The transcription factor PLZF is considered to be a master regulator of innate-like T cells, including NKT cells (Kovalovsky et al., 2008; Savage et al., 2008) and γδ T cells (Kreslavsky et al., 2009). We examined PLZF expression in mouse MAIT cells from spleens of B6 WT and Vα19 TCR transgenic.Cα−/− mice (Fig. 4 A). Whereas the WT MAIT cells were almost all PLZFhi, most of the TCR transgenic MAIT cells from spleen were PLZFlo, which is reminiscent of a previous study suggesting that Vα19 TCR transgenic.Cα−/− MAIT cells lacked this transcription factor (Martin et al., 2009). Interestingly, the percentage of Vα19 TCR transgenic MAIT cells that were PLZFhi was higher in lung (mean 61%) compared with spleen (mean 33%; Fig. 4 B). Nearly all (>95%) of the PLZFhi MAIT cells also expressed high levels of the memory T cell marker CD44, regardless of whether they were from WT or Vα19 TCR transgenic mice, whereas many but not all of the PLZFlo MAIT cells that were abundant in the TCR transgenic mice also lacked CD44 expression (Fig. 4, A and B).

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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Related in: MedlinePlus