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Published online before print September 8, 2004

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(Journal of Leukocyte Biology. 2004;76:1187-1199.)
© 2004 by Society for Leukocyte Biology

A novel epitope of N-CAM defines precursors of human adherent NK cells

Shen Li^*, Jun Xu^*, Valeria P. Makarenkova, Tjendimin Tjandrawan^*, Jukka Vakkila, Torsten Reichert, William Gooding, Carl F. Lagenaur, Cristian L. Achim^*, William H. Chambers^*,, Ronald B. Herberman^,¶, Theresa L. Whiteside^*, and Nikola L. Vujanovic^*,,1

^* Departments of Pathology,
Surgery,
Neurobiology, and ¶Medicine, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, Pennsylvania; and Department of Oral and Maxillofacial Surgery, University of Mainz, Germany

¹ Correspondence: University of Pittsburgh Cancer Institute, Hillman Cancer Center, G.17d, 5117 Centre Avenue, Pittsburgh, PA 15213-1863. E-mail: vujanovicnl{at}msx.upmc.edu

Activated, adherent natural killer (A-NK) cells represent a distinct subpopulation of interleukin (IL)-2-stimulated NK cells, which are selectively endowed with the increased expression of integrins and ability to adhere to solid surfaces, migrate into, infiltrate, and destroy cancerous tissues. The present study defines the phenotype and functions of precursors of A-NK (pre-A-NK) cells in humans. Peripheral blood pre-A-NK cells, in contrast to the rest of NK cells, express a novel epitope of CD56 neuronal cell adhesion molecule, termed ANK-1, and increased cell-surface levels of integrins. Pre-A-NK cells also express low levels of CD56 and CD161, and some express CD162 receptor, do not express CD25 or activation markers, and are effective mediators of NK cytotoxicity. Thus, pre-A-NK cells are generally similar to CD56^dim NK cells. However, pre-A-NK cells differ from the main NK cell subpopulation by having a lower expression level of CD16 and a lower ability to mediate redirected antibody-dependent, cell-mediated cytotoxicity. More importantly, pre-A-NK cells are preferentially endowed with the ability to rapidly respond to IL-2 by integrin-mediated adherence to endothelial cells, extracellular matrix, and plastic. This early, specific response of pre-A-NK cells to IL-2 is followed by their activation, vigorous proliferation, and differentiation into phenotypically and functionally similar A-NK cells. Pre-A-NK cells represent only 26% of peripheral blood NK cells but encompass the majority of NK cells in normal and cancerous, solid tissues. We conclude that pre-A-NK cells represent a distinct subset of resting, mature NK cells with the characteristics indicative of their ability to migrate and reside in solid tissues.

Key Words: NK cell subset • pre-A-NK cells • ANK-1 epitope • cell adherence • and tissue NK cells

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