NKp46+ CD3+ cells: a novel nonconventional T cell subset in cattle exhibiting both NK cell and T cell features

J Immunol. 2014 Apr 15;192(8):3868-80. doi: 10.4049/jimmunol.1302464. Epub 2014 Mar 17.

Abstract

The NKp46 receptor demonstrates a high degree of lineage specificity, being expressed almost exclusively in NK cells. Previous studies have demonstrated NKp46 expression by T cells, but NKp46+ CD3+ cells are rare and almost universally associated with NKp46 acquisition by T cells following stimulation. In this study we demonstrate the existence of a population of NKp46+ CD3+ cells resident in normal bovine PBMCs that includes cells of both the αβ TCR+ and γδ TCR+ lineages and is present at a frequency of 0.1-1.7%. NKp46+ CD3+ cells express transcripts for a broad repertoire of both NKRs and TCRs and also the CD3ζ, DAP10, and FcεR1γ but not DAP12 adaptor proteins. In vitro functional analysis of NKp46+ CD3+ cells confirm that NKp46, CD16, and CD3 signaling pathways are all functionally competent and capable of mediating/redirecting cytolysis. However, only CD3 cross-ligation elicits IFN-γ release. NKp46+ CD3+ cells exhibit cytotoxic activity against autologous Theileria parva-infected cells in vitro, and during in vivo challenge with this parasite an expansion of NKp46+ CD3+ cells was observed in some animals, indicating the cells have the potential to act as an anti-pathogen effector population. The results in this study identify and describe a novel nonconventional NKp46+ CD3+ T cell subset that is phenotypically and functionally distinct from conventional NK and T cells. The ability to exploit both NKRs and TCRs suggests these cells may fill a functional niche at the interface of innate and adaptive immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / genetics
  • CD3 Complex / metabolism*
  • Cattle
  • Cattle Diseases / immunology
  • Cattle Diseases / parasitology
  • Cytotoxicity, Immunologic
  • Gene Expression
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Natural Cytotoxicity Triggering Receptor 1 / genetics
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism*
  • Phenotype*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Natural Killer Cell / genetics
  • Receptors, Natural Killer Cell / metabolism
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • Theileria / immunology
  • Theileriasis / genetics
  • Theileriasis / immunology
  • Theileriasis / metabolism

Substances

  • CD3 Complex
  • Natural Cytotoxicity Triggering Receptor 1
  • Receptors, Antigen, T-Cell
  • Receptors, Natural Killer Cell
  • Interferon-gamma