Eomes expression reports the progressive differentiation of IFN-γ-producing Th1-like γδ T cells
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Eomes expression reports the progressive differentiation of IFN-γ-producing Th1-like γδ T cells. / Lino, Ciro N R; Barros-Martins, Joana; Oberdörfer, Linda; Walzer, Thierry; Prinz, Immo.
In: EUR J IMMUNOL, Vol. 47, No. 6, 06.2017, p. 970-981.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Eomes expression reports the progressive differentiation of IFN-γ-producing Th1-like γδ T cells
AU - Lino, Ciro N R
AU - Barros-Martins, Joana
AU - Oberdörfer, Linda
AU - Walzer, Thierry
AU - Prinz, Immo
N1 - © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2017/6
Y1 - 2017/6
N2 - The transcription factor Eomesodermin (Eomes) plays a crucial role in regulating cytotoxic function, development, and survival of immune cells. γδ T cells can express Eomes, but its contribution to their differentiation is unknown. Using Eomes-IRES-GFP mice, we show that Eomes+ γδ T cells are unequally distributed among organs, with the highest proportion in spleen. While the majority of Eomes+ γδ T cells expressed Vγ1+ and Vγ4+ TCRs, Eomes was absent in Vγ5+ , Vγ6+ , and Vγ7+ subsets. Moreover, Eomes was co-expressed in γδ T cells with Th1 lineage-related factors such as CD27, T-bet, and Ly6C, but not with Th17 lineage-related genes. Eomes+ and Eomes- γδ T-cell populations showed distinct gene expression profiles, with an increase of cytotoxic-related genes in Eomes+ γδ T cells. Furthermore, Eomes could be induced in peripheral γδ T cells by IL-12 and IL-4, and Eomes+ γδ T cells presented a higher proliferation rate and IFN-γ production when stimulated in vitro with IL-12 and IL-18. However, γδ T cells with very high Eomes levels displayed an exhausted phenotype with high levels of PD-1, and were less capable of IFN-γ production. Together, this study highlights Eomes as a marker for the differentiation of Th1-like effector γδ T cells.
AB - The transcription factor Eomesodermin (Eomes) plays a crucial role in regulating cytotoxic function, development, and survival of immune cells. γδ T cells can express Eomes, but its contribution to their differentiation is unknown. Using Eomes-IRES-GFP mice, we show that Eomes+ γδ T cells are unequally distributed among organs, with the highest proportion in spleen. While the majority of Eomes+ γδ T cells expressed Vγ1+ and Vγ4+ TCRs, Eomes was absent in Vγ5+ , Vγ6+ , and Vγ7+ subsets. Moreover, Eomes was co-expressed in γδ T cells with Th1 lineage-related factors such as CD27, T-bet, and Ly6C, but not with Th17 lineage-related genes. Eomes+ and Eomes- γδ T-cell populations showed distinct gene expression profiles, with an increase of cytotoxic-related genes in Eomes+ γδ T cells. Furthermore, Eomes could be induced in peripheral γδ T cells by IL-12 and IL-4, and Eomes+ γδ T cells presented a higher proliferation rate and IFN-γ production when stimulated in vitro with IL-12 and IL-18. However, γδ T cells with very high Eomes levels displayed an exhausted phenotype with high levels of PD-1, and were less capable of IFN-γ production. Together, this study highlights Eomes as a marker for the differentiation of Th1-like effector γδ T cells.
KW - Animals
KW - Cell Differentiation/genetics
KW - Cytokines/immunology
KW - Interferon-gamma/biosynthesis
KW - Interleukin-12/immunology
KW - Interleukin-18/immunology
KW - Interleukin-4/immunology
KW - Mice
KW - Mice, Inbred C57BL
KW - Receptors, Antigen, T-Cell, gamma-delta/immunology
KW - T-Box Domain Proteins/genetics
KW - T-Lymphocyte Subsets/immunology
KW - Th1 Cells/immunology
KW - Th17 Cells/immunology
U2 - 10.1002/eji.201646753
DO - 10.1002/eji.201646753
M3 - SCORING: Journal article
C2 - 28386934
VL - 47
SP - 970
EP - 981
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 6
ER -
