Unique features of naive CD8+ T cell activation by IL-2

J Immunol. 2013 Dec 1;191(11):5559-73. doi: 10.4049/jimmunol.1302293. Epub 2013 Oct 28.

Abstract

IL-2 has a pervasive influence on the immune system and dictates the survival and differentiation of multiple T cell subsets, including CD4 regulatory T cells, CD4 Th cells, and CD8 memory cells. IL-2 is synthesized by T cells during the early stages of the immune response and promotes T cell expansion and effector cell generation after initial activation via TCR signaling. Based on studies with activated T cell lines maintained in vitro, IL-2 is known to activate multiple signaling pathways that show considerable overlap with the pathways elicited via the TCR. In this paper, we have examined IL-2 signaling under TCR-independent conditions, namely by culturing purified resting naive CD8 T cells with IL-2 in the absence of Ag or APC. Under these conditions, we show in this study that IL-2 elicits a unique pattern of signaling associated with strong lymphocyte-specific protein tyrosine kinase/JAK3-dependent activation of the PI3K/AKT pathway with little or no involvement of STAT5, NF-κB, or the calcineurin/NFAT pathways. Such signaling induces marked proliferation associated with rapid and selective expression of eomesodermin but not T-bet and differentiation into long-lived central memory cells after adoptive transfer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic / genetics
  • Immunologic Memory / genetics
  • Interleukin-2 / immunology*
  • Janus Kinase 3 / genetics
  • Janus Kinase 3 / metabolism*
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oncogene Protein v-akt / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction / genetics
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology*
  • Th1-Th2 Balance

Substances

  • Cytokines
  • Eomes protein, mouse
  • Interleukin-2
  • T-Box Domain Proteins
  • Phosphatidylinositol 3-Kinases
  • Janus Kinase 3
  • Oncogene Protein v-akt