NKp46+CD3+ cells - a novel non-conventional T-cell subset in cattle exhibiting both NK cell and T-cell features

• Published in: The Journal of immunology (1950) 2014-03, Vol.192 (8), p.3868-3880
• Main Authors: Connelley, Timothy K., Longhi, Cassandra, Burrells, Alison, Degnan, Kathryn, Hope, Jayne, Allan, Alasdair, Hammond, John A., Storset, Anne K., Morrison, W. Ivan
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1302464

The NKp46 receptor demonstrates a high degree of lineage-specificity, being expressed almost exclusively in natural killer 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 PBMC which include 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 natural killer (NKR) and T-cell receptors (TCR) 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 signalling pathways are all functionally competent and capable of mediating-re-direct 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 presented herein identifies and describes a novel non-conventional NKp46 + CD3 + T-cell subset that is phenotypically and functionally distinct from conventional NK and T-cells. The ability to exploit both NKR and TCR suggests these cells may fill a functional niche at the interface of innate and adaptive immune responses.