title: Interleukin-4 regulates eomesodermin in CD8+ T cell development and differentiation.
abstract: Interleukin (IL)-4 is a cytokine classically associated with CD4(+) T helper type 2 differentiation, but has been recently shown to also be required for the development of CD8(+) innate-like lymphocytes. CD8(+) innate-like lymphocytes are non-conventional lymphocytes that exhibit characteristics typically associated with memory CD8(+) T cells, including expression of the T-box transcription factor Eomesodermin (Eomes). Here we investigate the signaling pathways required for IL-4 induction of Eomes and CD8(+) innate-like lymphocyte markers in murine CD8SP thymocytes and peripheral CD8(+) T cells. We demonstrate that IL-4 is sufficient to drive Eomes expression and the CD8(+) innate-like lymphocyte phenotype through cooperation between STAT6- and Akt-dependent pathways. Furthermore, we show that while IL-4 has little effect on the induction of Eomes in the setting of robust T cell receptor (TCR) activation, this cytokine promotes Eomes in the setting of attenuated TCR stimulation in mature CD8(+) T cells suggesting that cytokine signaling pathways may direct cell fate when TCR signals are limiting.
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Shannon A
authors.initials: SA
authors.lastname: Carty
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Koretzky
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Martha S
authors.initials: MS
authors.lastname: Jordan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020825:T-Box Domain Proteins / Q000378:metabolism*; D060168:Thymocytes / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C491198:Eomes protein, mouse; D011948:Receptors, Antigen, T-Cell; D050800:STAT6 Transcription Factor; D020825:T-Box Domain Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D051057:Proto-Oncogene Proteins c-akt