THE EFFECT OF NK CELL ACTIVATION BY TUMOR-CELLS ON ANTIGEN-SPECIFIC ANTIBODY-RESPONSES

In addition to mediating direct cytotoxicity, NK cells can exert regul atory effects on specific immune responses. For example, injection of poly (I:C) can alter specific Ab responses, which is attributable to t he production of IFN-gamma by NK cells. To test whether direct activat ion of NK cells can exert the same effect, we have injected, at the sa me time as Ag challenge, BCL1-C11 tumor cells, which are highly effect ive inducers of IFN-gamma production by NK cells. The results show a s pecific enhancement of the IgG2a response, which does not occur with a tumor (70Z/3) that does not induce IFN-gamma production, This enhance ment is NK cell and IL-12 dependent. However, BCL1-C11 cells cannot di rectly induce IL-12 production in peritoneal exudate cells (PECs), On the other hand, PECs from tumor-treated mice produce IL-12 in response to LPS, suggesting that they are primed in vivo, Furthermore, the IL- 12 production is NK cell and IFN-gamma dependent, These results indica te that if tumor cells can directly activate NK cells to produce IFN-g amma, this cytokine initiates an amplification loop by activating macr ophages to produce IL-12, which in turn activates NK cells further, re sulting in the alteration of the isotype distribution of specific Ab r esponses. Production of the appropriate Ab isotype should enhance Ab-d ependent cellular cytotoxicity against targets mediated by NK cells, i mplicating their role(s) in the specific immune response as well as th e initial nonspecific phase.