1. Protein kinase C and cytokine regulation of CD3-AK response induced by alphaCD3. Induction of CD3-AK killer cells is predominantly a PKC-dependent event; however, there is a PKC-independent pathway of CD3-AK cell generation regulated by IL-4. In the PKC-dependent pathway, PKC regulates the production of cytolytic granules but does not directly affect the lytic activity of these granules. In the PKC-independent pathway, IL-4 is the major lymphokine which regulates the production of cytolytic granules. IL-2 regulates both the cytolytic activity and the growth of CD3-AK cells in the PKC-dependent pathway of CD3-AK response. In the PKC-independent pathway, the major role of IL-2 is to support the growth of CD3-AK cells. 2. Differential regulation by cytokines and PKC of the proliferative and cytotoxic responses to alphaCD3 activation of resting lymphocytes and preactivated lymphocytes. IL-4 up-regulates the cytotoxic response but down-regulates the proliferation of CD3-AK cells. Generation of CD3-AK killer cells in resting lymphocytes is susceptible to the inhibition by PKC antagonist at non-toxic doses which does not significantly affect their proliferative response. The reverse is true for the preactivated CD3-AK cells.
