NCR1 is an activating receptor expressed on a subset of canine NK cells

Abstract

Defining NK cells has been challenging in many veterinary species. Although several groups have described putative NK cell populations, there is still no consensus on a definition of NK cells in the dog. In the present study, canine NK cells are characterized as CD3−GranzymeB+ cells, further divided into a NCR1+ and a NCR1− subset. All dogs examined displayed both subsets in blood, although of quite variable magnitude. Following vaccination an increase was observed in the CD3− NCR1− cell population in blood, but not in the CD3− NCR1+ population. Non-B non-T cell cultures stimulated with IL-2 and IL-15 were dominated by CD3−GranzymeB+ cells after approximately 2 weeks and a large proportion of the CD3−GranzymeB+ cells expressed NCR1. IL-12 stimulation lead to a further upregulation resulting in an almost uniform expression of NCR1. The cultured cells expressed MHC class II, showed a variable expression of CD8 and were negative for CD4 and CD21. The cultures were able to kill known NK cell targets, and NCR1 was shown to be a major activating receptor. A large proportion of the NCR1+ cells, but none of the NCR1− cells, produced IFNγ in response to IL-12 stimulation. These results show that NCR1 defines two subsets of canine NK cells, likely to represent different activation stages, and that NCR1 acts as an activating receptor on canine NK cells.