Cytokine- and TCR-Mediated Regulation of T Cell Expression of Ly6C and Sca-1

J Immunol. 2018 Mar 1;200(5):1761-1770. doi: 10.4049/jimmunol.1701154. Epub 2018 Jan 22.

Abstract

Ly6C and Sca-1 (Ly6A/E) are Ly6 family GPI-anchored surface molecules that are differentially expressed by multiple immune populations. Ly6C expression has been used to distinguish short-lived effector CD4+ T cells from memory precursor effector cells, whereas Sca-1 has been used in the identification of CD8+ memory stem cells. This study examines the expression patterns of these molecules and establishes that, in vitro, IL-27, type I IFN, and IFN-γ are potent inducers of Ly6C and Sca-1 in naive mouse CD4+ and CD8+ T cells, whereas TGF-β limits their expression. The induction of Ly6C and Sca-1 by IL-27 and IFN-γ is dependent on STAT1, but not STAT3 or T-bet. In mouse splenocytes, at homeostasis, Ly6C and Sca-1 expression was not restricted to effector cells, but was also found at various levels on naive and memory populations. However, in response to infection with Toxoplasma gondii, pathogen-specific T cells expressed high levels of these molecules and in this context, endogenous IL-27 and IFN-γ were required for the expression of Ly6C but not Sca-1. Together, these findings highlight the TCR-dependent and cytokine-mediated signals that modulate T cell expression of Ly6C and Sca-1 in vitro and in vivo during infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cytokines / immunology*
  • Female
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell / immunology*
  • Toxoplasma / immunology
  • Toxoplasmosis / immunology

Substances

  • Antigens, Ly
  • Cytokines
  • Ly-6C antigen, mouse
  • Ly6a protein, mouse
  • Membrane Proteins
  • Receptors, Antigen, T-Cell