Available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/dci Natural killer cells in lymph nodes of healthy calves express CD16 and show both cytotoxic and cytokine-producing properties Preben Boysen a,Ã , Gjermund Gunnes b , Daniela Pende c , Mette Valheim d , Anne K. Storset a a Department of Food Safety and Infection Biology, Norwegian School of Veterinary Science, P.O. Box 8146 Dep., N-0033 Oslo, Norway b Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, P.O. Box 8146 Dep., N-0033 Oslo, Norway c Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy d Department for Animal Health, Section for Pathology, National Veterinary Institute, P.O. Box 8156 Dep., N-0033 Oslo, Norway Received 23 October 2006; received in revised form 30 October 2007; accepted 17 November 2007 Available online 18 December 2007 KEYWORDS Natural killer cells (NK cells); Lymph nodes/ lymphoid organs; Animal models; Cattle/bovine; Phenotype/cell markers; Cytotoxicity; Cytokines; Interferon-gamma Summary Natural killer (NK) cells were recently shown to play an important immunomodulatory role in lymph nodes. We here report the presence, phenotype and function of NK cells resident in lymph nodes of several anatomical sites of healthy calves. NKp46 + /CD3  lymphocytes, recently demonstrated to precisely identify NK cells in all tested species, were present in the paracortex and the medulla of bovine lymph nodes. Most lymph node-derived NK cells expressed CD16 and perforin, and a lytic capacity was demonstrated, while a well- developed interferon-gamma response to interleukin-2 and interleukin-12 stimulation was also seen. Lymph node-derived NK cells differed from those in blood by a higher expression of the activation markers CD44 and CD25, as well as CD8. L-selectin (CD62L) was expressed by the majority of lymph node-derived NK cells, consistent with a dependency of this molecule for migration to lymph nodes. Unlike in blood, the majority of lymph node NK cells had little or no CD2 expression. Compared to available literature, calf lymph nodes contained NK cells in numbers equal to or higher than reported in humans, and clearly higher than in mice. These findings suggest a cytotoxic role of lymph node residing NK cells, beyond the predominantly cytokine-producing role previously inferred from studies on human NK cells. & 2007 Elsevier Ltd. All rights reserved. ARTICLE IN PRESS 0145-305X/$ - see front matter & 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.dci.2007.11.006 Ã Corresponding author. Tel.: +4722964817; fax: +4722964818. E-mail address: preben.boysen@veths.no (P. Boysen). Developmental and Comparative Immunology (2008) 32, 773–783