INCREASED IL-12 P40 HOMODIMER SECRETION BY SPLEEN-CELLS DURING IN-VIVO GROWTH OF THE BW-19 T-CELL HYBRIDOMA ACCOMPANIES SUPPRESSION OF NATURAL IMMUNITY

The high capacity of the T cell hybridoma BW-19 to metastasize to the spleen, despite its high and moderate sensitivity to lysis by macropha ges and natural killer (NK) cells, respectively appears to be linked t o its capacity to suppress local resident NK cell and macrophage activ ity. Such suppression of splenic NK cell and macrophage activity is ac companied by an increased production of the p40 subunit of interleukin -12 (IL-12) by spleen cells. Closer examination revealed that most of the p40 subunit is present under the form of the homodimer (p40)(2), w hereas the heterodimeric form of IL-12 is present only in small amount s. Since (p40)2 is known to be a strong antagonist of IL-12-mediated e ffects, i.e., NK cell activation and interferon-gamma (IFN-gamma) secr etion, the increased production of (p40)2 after BW-19 cell inoculation may contribute to the suppression of NK cell and macrophage activity. In addition, we found that the high production of (p40)2 in our tumor model was accompanied by a drastic decrease in IL-2 and IFN-gamma pro duction by spleen cells, further favoring the possibility that (p40)2 plays a role in the suppression of NK cell and macrophage cytotoxicity . Our results show that normal spleen cells can produce (p40)2 in resp onse to cancer cell growth in vivo and are highly suggestive of a role for (p40)(2) in the suppression of natural immunity. (C) 1998 Wiley-L iss, Inc.