NK cytokine secretion and cytotoxicity occur independently of the SLP-76 adaptor protein

The adapter protein SLP-76 is required for T cell development and TCR signa l transduction. SLP-76 is also expressed in NK cells, yet splenic populatio ns of NK cells develop normally in SLP-76(-/-) deficient mice. We examined the effects of SLP-76 deficiency upon cellular activation through studies o f NK function in SLP-76(-/-) mice. This study presents evidence that NK pop ulations in both spleen and liver of SLP-76(-/-) mice remain intact. Natura l cytotoxic responses of SLP-76(-/-) splenocytes proceed in a manner compar able to those of wild-type control splenocytes. Similar to controls, SLP-76 (-/-) splenocytes exhibit enhanced survival and augmented cytotoxic capacit y after in vitro culture with IL-2. IL-2-stimulated SLP-76(-/-) splenocytes also retain normal antibody-dependent cellular cytotoxicity and the abilit y to secrete IFN-gamma in response to IL-12 stimulation. These results indi cate that, unlike events stimulated by TCR engagement, signaling cascades e ngaged by IL-2 and IL-12 receptors, by Fc gamma RIIIA (which mediates antib ody-dependent cellular cytotoxicity), and by natural cytotoxicity-associate d receptors on murine NK cells can occur independently of SLP-76.