CD38 triggers cytotoxic responses in activated human natural killer cells

Receptors used by natural killer (NK) cells to mediate natural cytotoxicity are poorly defined, although it is now clear that a number of adhesion mol ecules can serve this function. CD38 transduces signals on T- and B-cell li nes, and we asked whether it could trigger lytic and secretory responses in human NK cells. By using an anti-CD38 monoclonal antibody in reverse antib ody-dependent cellular cytotoxicity experiments, it is shown that CD38 enga gement triggers cytotoxic responses by activated NK cells, but not by cytot oxic T lymphocytes or fresh NK cells. Cross-linking with anti-CD38 F(ab')(2 ) caused activated NK cells to release granzymes and cytokines, but did not trigger an increase in intracellular Ca2+. Fresh NK cells acquired CD38-de pendent lytic function during activation with interleukin-2 (IL-2), and inh ibitor studies suggested that IL-2 stimulated the de novo expression of pro teins that act between CD38 and the lytic machinery in NK cells. The induct ion of proteins that link commonly expressed adhesion molecules to effector mechanisms could provide a paradigm for pathogen recognition by the innate immune system. This is a US government work. There are no restrictions on its use.