Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8(+) T cells

Nat Commun. 2015 May 8;6:7089. doi: 10.1038/ncomms8089.

Abstract

CD8(+) T-cell memory phenotype and function are acquired after antigen-driven activation. Memory-like cells may also arise in absence of antigenic exposure in the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription factor for the development of these unconventional memory cells. Herein, we show that type I interferon signalling in CD8(+) T cells directly activates Eomes gene expression. Consistent with this observation, the phenotype, function and age-dependent expansion of 'virtual memory' CD8(+) T cells are strongly affected in absence of type I interferon signalling. In addition, type I interferons induce a sustained expansion of 'virtual memory' CD8(+) T cells in an Eomes-dependent fashion. We further show that the development of 'innate thymic' CD8(+) T cells is dependent on the same pathway. In conclusion, we demonstrate that type I interferon signalling in CD8(+) T cells drives Eomes expression and thereby regulates the function and homeostasis of memory-like CD8(+) T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / metabolism
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism*
  • Gene Expression Regulation / drug effects
  • Homeostasis / drug effects
  • Immunity, Innate / drug effects
  • Immunologic Memory / drug effects
  • Immunologic Memory / genetics*
  • Interferon Type I / metabolism*
  • Interferon-Stimulated Gene Factor 3, gamma Subunit / metabolism
  • Interferon-gamma / biosynthesis
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Poly I-C / pharmacology
  • Receptor, Interferon alpha-beta / deficiency
  • Receptor, Interferon alpha-beta / metabolism
  • Signal Transduction / drug effects
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / metabolism
  • Thymocytes / drug effects
  • Thymocytes / metabolism

Substances

  • Antigens
  • Eomes protein, mouse
  • IRF9 protein, mouse
  • Ifnar1 protein, mouse
  • Interferon Type I
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • T-Box Domain Proteins
  • Receptor, Interferon alpha-beta
  • Interferon-gamma
  • Poly I-C