Interleukin-4 regulates eomesodermin in CD8+ T cell development and differentiation

• Published in: PloS one Vol. 9; no. 9; p. e106659
• Main Authors: Carty, Shannon A, Koretzky, Gary A, Jordan, Martha S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.09.2014; Public Library of Science (PLoS)
• Subjects: AKT protein; Animals; Biology and life sciences; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - metabolism; Cell activation; Cell Differentiation - drug effects; Cell fate; Cytokines; Differentiation; Drug dosages; Flow cytometry; Gene expression; Immunological memory; Immunology; Interferon-gamma - metabolism; Interleukin 4; Interleukin-4 - pharmacology; Laboratories; Lymphocytes; Lymphocytes T; Medicine; Memory cells; Mice; Phenotype; Phenotypes; Proto-Oncogene Proteins c-akt - metabolism; Receptors, Antigen, T-Cell - metabolism; Research and Analysis Methods; Signal transduction; Signal Transduction - drug effects; Signaling; Stat6 protein; STAT6 Transcription Factor - metabolism; T cell receptors; T-Box Domain Proteins - metabolism; T-cell receptor; Thymocytes; Thymocytes - immunology; Transcription factors; Up-Regulation - drug effects; New York; United States > US; Baltimore Maryland; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106659

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.