SLAMF7 and IL-6R define distinct cytotoxic versus helper memory CD8+ T cells

Nat Commun. 2020 Dec 11;11(1):6357. doi: 10.1038/s41467-020-19002-6.

Abstract

The prevailing 'division of labor' concept in cellular immunity is that CD8+ T cells primarily utilize cytotoxic functions to kill target cells, while CD4+ T cells exert helper/inducer functions. Multiple subsets of CD4+ memory T cells have been characterized by distinct chemokine receptor expression. Here, we demonstrate that analogous CD8+ memory T-cell subsets exist, characterized by identical chemokine receptor expression signatures and controlled by similar generic programs. Among them, Tc2, Tc17 and Tc22 cells, in contrast to Tc1 and Tc17 + 1 cells, express IL-6R but not SLAMF7, completely lack cytotoxicity and instead display helper functions including CD40L expression. CD8+ helper T cells exhibit a unique TCR repertoire, express genes related to skin resident memory T cells (TRM) and are altered in the inflammatory skin disease psoriasis. Our findings reveal that the conventional view of CD4+ and CD8+ T cell capabilities and functions in human health and disease needs to be revised.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Ligand / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Gene Expression
  • Humans
  • Immunity, Cellular
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Interleukin-6 / genetics
  • Receptors, Interleukin-6 / metabolism*
  • Signaling Lymphocytic Activation Molecule Family / genetics
  • Signaling Lymphocytic Activation Molecule Family / metabolism*
  • Skin / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Chemokines
  • Cytokines
  • Receptors, Interleukin-6
  • SLAMF7 protein, human
  • Signaling Lymphocytic Activation Molecule Family
  • CD40 Ligand