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The Journal of Immunology, Vol 153, Issue 10 4399-4407, Copyright © 1994 by American Association of Immunologists
ARTICLES |
R Galandrini, R De Maria, M Piccoli, L Frati and A Santoni
Department of Experimental Medicine, La Sapienza, University of Rome, Italy.
CD44, a major hyaluronate receptor, is involved in a variety of lymphocyte functions including lympho-hemopoiesis, adhesion to high endothelial venules or the extracellular matrix, and T cell activation. Here we investigated the ability of CD44 to affect the cytotoxic functions of human NK cells. Ligation of CD44 by selected mAb (J173 and F10442) resulted in a rapid, dose-response-dependent enhancement of NK cytotoxic activity against a panel of tumor target cells that varied in their sensitivity to NK killing. Neither enhanced killing against NK- resistant target cells nor CD44 mAb-mediated redirected lysis was not observed. CD44 cross-linking also was found to up-regulate CD16- mediated lysis. In an attempt to investigate the early biochemical events that occur after CD44 ligation, we found that optimal cross- linking conditions induce a rapid increase of intracellular free calcium levels, which is abrogated by extracellular Ca2+ chelation. Moreover, enhanced and more sustained Ca2+ rise resulted from CD16 and CD44 coengagement. In contrast, no inositol 1,4,5-trisphosphate generation was found after optimal CD44 cross-linking. These results suggest that although CD44 is not capable of delivering a lytic signal in human NK cells, it coactivates spontaneous or CD16-mediated NK cytotoxicity. The variation in intracellular free calcium may be one of the signals that account for the costimulation of the lytic activity.
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