A novel functional cell surface dimer (Kp43) expressed by natural killer cells and gamma/delta TCR+ T lymphocytes. II. Modulation of natural killer cytotoxicity by anti-Kp43 monoclonal antibody.
In the present study we provide the first evidence supporting the fact that the Kp43 NK-associated cell-surface dimer may be involved in regulating MHC-unrestricted cytotoxicity. Our results indicated that incubation of IL-2-activated NK cells in a 51Cr-release assay with either the Kp43-specific mAb or its F(ab')2 fragments induced a significant cytolytic activity directed against normal autologous and allogeneic T cell blasts, which are relatively resistant to NK cell-mediated lysis. The cytotoxic effect was not observed in fresh CD3- CD16+ CD56+ Kp43+ lymphocytes and was only substantiated in IL-2-preactivated NK cells. Although stimulation with the Kp43-specific mAb did not significantly change the intracellular Ca2+ concentration, both Ca2+ and Mg2+ were required for the induction of cytotoxicity. The anti-Kp43-mediated activation of cytolysis was inhibited by anti-CD18 and CD11a mAb, whereas it was not significantly altered by either CD11b, CD11c, CD2, or LFA-3-specific mAb, rendering unlikely the participation of the latter. In contrast to these results the Kp43-specific mAb did not enhance the high levels of spontaneous cytotoxicity mediated by IL-2-activated NK cells against a panel of different tumor cell lines. An inhibitory effect mediated by anti-Kp43 mAb on the IL-2-dependent proliferation of NK cells was previously reported and appears, at least partially, secondary to the induction of an autolytic mechanism that is synergistically enhanced by anti-CD16 mAb. Altogether our results point out that interaction of the Kp43 dimer with its specific mAb is capable of inducing cytolytic activity and suggest that the molecule may play an important functional role in lymphokine-activated NK cells.
Aramburu
J
J
Sección de Inmunologia, Hospital de la Princesa, Madrid, Spain.
Balboa
M A
MA
Izquierdo
M
M
López-Botet
M
M
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000502:physiology; D000954:Antigens, Surface / Q000737:chemistry / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002413:Cations, Divalent; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D015394:Molecular Structure; D011961:Receptors, Fc / Q000502:physiology; D017452:Receptors, IgG; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D002413:Cations, Divalent; D016169:Lymphocyte Function-Associated Antigen-1; D011961:Receptors, Fc; D017452:Receptors, IgG; D002118:Calcium