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J Immunol. 2015 Nov 15;195(10):4742-52. doi: 10.4049/jimmunol.1501159. Epub 2015 Oct 9.

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction.

Author information

1
Max-Planck-Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany; Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, D-79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, D-79104 Freiburg, Germany;
2
Max-Planck-Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany; Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, D-79106 Freiburg, Germany;
3
INSERM, U1043, Toulouse, F-31300, France; Centre National de la Recherche Scientifique, U5282, Toulouse, F-31300, France; Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France;
4
Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, D-79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, D-79104 Freiburg, Germany;
5
Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, D-79106 Freiburg, Germany;
6
University Medical Centre, Renal Department, Centre for Clinical Research, D-79106 Freiburg, Germany; BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University, D-79104 Freiburg, Germany; and Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, D-79102 Freiburg, Germany.
7
Max-Planck-Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany; Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, D-79106 Freiburg, Germany; izcue@ie-freiburg.mpg.de.

Abstract

CD4(+) T cells polarize into effector Th subsets characterized by signature transcription factors and cytokines. Although T-bet drives Th1 responses and represses the alternative Th2, Th17, and Foxp3(+) regulatory T cell fates, the role of the T-bet-related transcription factor eomesodermin (Eomes) in CD4(+) T cells is less well understood. In this study, we analyze the expression and effects of Eomes in mouse CD4(+) T lymphocytes. We find that Eomes is readily expressed in activated CD4(+) Th1 T cells in vivo. Eomes(+) CD4(+) T cells accumulated in old mice, under lymphopenic conditions in a T cell transfer model of colitis, and upon oral Ag administration. However, despite its expression, genetic deletion of Eomes in CD4(+) T cells did not impact on IFN-γ production nor increase Th2 or Th17 responses. In contrast, Eomes deficiency favored the accumulation of Foxp3(+) cells in old mice, after in vivo differentiation of Eomes-deficient naive CD4(+) T cells, and in response to oral Ag in a cell-intrinsic way. Enforced Eomes expression during in vitro regulatory T cell induction also reduced Foxp3 transcription. Likewise, bystander Eomes-deficient CD4(+) T cells were more efficient at protecting from experimental autoimmune encephalitis compared with wild-type CD4(+) T cells. This enhanced capacity of Eomes-deficient CD4(+) T cells to inhibit EAE in trans was associated with an enhanced frequency of Foxp3(+) cells. Our data identify a novel role for Eomes in CD4(+) T cells and indicate that Eomes expression may act by limiting Foxp3 induction, which may contribute to the association of EOMES to susceptibility to multiple sclerosis.

PMID:
26453746
DOI:
10.4049/jimmunol.1501159
[Indexed for MEDLINE]
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