title: Eomes expression reports the progressive differentiation of IFN-γ-producing Th1-like γδ T cells.
abstract: 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.
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.|CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.
authors.forename: Ciro N R
authors.initials: CNR
authors.lastname: Lino
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Joana
authors.initials: J
authors.lastname: Barros-Martins
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Oberdörfer
authors.affiliation: Centre International de Recherche en Infectiologie, Ecole Normale Supérieure, Université de Lyon, Lyon, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Walzer
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Immo
authors.identifier: 0000-0002-8789-9578
authors.initials: I
authors.lastname: Prinz
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D016207:Cytokines / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; C491198:Eomes protein, mouse; D020382:Interleukin-18; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020825:T-Box Domain Proteins; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Cell differentiation; Cytokines; Developmental immunology; Transcription factors; g/d T cells