Natural killer (NK) cells have not previously been precisely identified or characterized in cattle or any other ruminant species. We have generated a monoclonal antibody against bovine NKp46, which is expressed exclusively by NK cells in man. NKp46 + cells comprised 1-10% of blood mononuclear cells in cattle, and did not stain with antibodies against CD3, CD4, TCR1, B cell or granulocyte markers. The majority of the NKp46 + cells expressed CD2, and a variable fraction also expressed CD8. The tissue distribution of NKp46 + cells in cattle was compatible with the tissue distribution of NK cells in other species. Bovine NKp46 + cells had typical, large granular lymphocyte morphology, and proliferated vigorously in response to bovine IL-2 for a limited number of cell divisions. IL-2-activated NKp46 + cells killed the bovine kidney cell line MDBK. This cytotoxicity was inhibited by preincubation with antibody against NKp46. In a redirected lysis assay, IL-2-activated NKp46 + cells killed the Fc + R + target cell line P815 after preincubation with antibody against NKp46. Together, these data indicate that bovine NKp46 is an activating receptor and demonstrate the existence of a subset of leukocytes in cattle that, in terms of surface markers, morphology and function, represent NK cells.

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Background: Natural killer (NK) cells in the cow have been elusive due to the lack of specific NK cell markers, and various criteria including a CD3 -/CD2 + phenotype have been used to identify such cells. The recent characterization of the NK-specific NKp46 receptor has allowed a more precise definition of bovine NK cells. NK cells are known as a heterogeneous cell group, and we here report the first functional study of bovine NK cell subsets, based on the expression of CD2.