KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations in humans

Cell Rep. 2023 Mar 28;42(3):112236. doi: 10.1016/j.celrep.2023.112236. Epub 2023 Mar 9.

Abstract

Subsets of the human CD8+ T cell population express inhibitory NK cell receptors, such as killer immunoglobulin-like receptors (KIRs) and NKG2A. In the present study, we examine the phenotypic and functional characteristics of KIR+CD8+ T cells and NKG2A+CD8+ T cells. KIRs and NKG2A tend to be expressed by human CD8+ T cells in a mutually exclusive manner. In addition, TCR clonotypes of KIR+CD8+ T cells barely overlap with those of NKG2A+CD8+ T cells, and KIR+CD8+ T cells are more terminally differentiated and replicative senescent than NKG2A+CD8+ T cells. Among cytokine receptors, IL12Rβ1, IL12Rβ2, and IL18Rβ are highly expressed by NKG2A+CD8+ T cells, whereas IL2Rβ is expressed by KIR+CD8+ T cells. IL-12/IL-18-induced production of IFN-γ is prominent in NKG2A+CD8+ T cells, whereas IL-15-induced NK-like cytotoxicity is prominent in KIR+CD8+ T cells. These findings suggest that KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations with different cytokine responsiveness.

Keywords: CD8(+) T cells; CP: Immunology; KIR; NKG2A; innate-like T cells; killer immunoglobulin-like receptor; virtual memory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes*
  • Humans
  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, Immunologic*
  • Receptors, KIR
  • Receptors, Natural Killer Cell

Substances

  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, Natural Killer Cell
  • KLRC1 protein, human