CD69 is a stimulatory receptor for natural killer cell and its cytotoxic effect is blocked by CD94 inhibitory receptor

CD69 is a differentiation antigen expressed shortly after activation on T l ymphocytes and other cells of haematopoietic origin, including natural kill er (NK) cells. The function of CD69 on T lymphocytes acting as a costimulat ory molecule in proliferation and lymphokine secretion is well established. NK cells express CD69 after activation by different stimuli such as phorbo l 12-myristate 13-acetate (PMA), interleukin (IL)-2, IL-12, interferon-alph a (IFN-alpha) or anti-CD16 monoclonal antibodies (mAbs). However, although it has been shown that CD69 triggers NK-cell-mediated cytolytic activity, i ts effect on other NK-cell functions has not been studied. Furthermore, the possible interaction of CD69 triggering with other C-lectin type inhibitor y receptors is not known. Thus, the objective of this work is to determine whether CD69-mediated NK cytotoxicity can be regulated by CD93 inhibitory r eceptor and the role of CD69 on other NK-cell functions different of cytoto xicity. The results show that CD69-mediated NK cytotoxicity can be abrogate d by CD93 stimulation in NK cells expressing the CD94 inhibitory form of th e receptor, indicating that CD94 regulates the cytotoxic events initiated b y a wide variety of NK activatory receptors. We also show that anti-CD69 mA bs, not only triggered NK cytotoxicity, but also induce NK-cell proliferati on, CD25 and intracellular adhesion molecule-1 (ICAM-1) expression, TNF-alp ha production and Ca2+ mobilization in preactivated NK cells. These results suggest that CD69 plays a crucial role in NK-cell function contributing to sustain NK-cell activation, as it has been previously demonstrated in T ce lls.