NATURAL-KILLER-CELLS INHIBIT THE DEVELOPMENT OF AUTOANTIBODY PRODUCTION IN (C57BL 6XDBA/2) F1-HYBRID MICE INJECTED WITH DBA/2 SPLEEN-CELLS/

We investigated the role of natural killer (NK) cells in the developme nt of autoantibody production in which (C57BL/6 X DBA/2) F1 (BDF1) hyb rid mice were injected intravenously with spleen cells (SC) from paren tal DBA/2 mice (treated BDF1 mice). Treated BDF1 mice began to show an increase in serum anti-dsDNA antibody 2 weeks after injection, while the NK activity of their SC transiently increased initially in the fir st 1 to 2 weeks after injection, but subsequently decreased dramatical ly. Flow cytometric analysis suggested that this sequential change in NK activity correlated with the absolute number of host-derived NK1.1( +) cells in SC from treated BDF1 mice. We demonstrated that the level of anti-dsDNA in serum is directly influenced by the level of NK activ ity in treated BDF1 mice. Depletion of NK cells by administration of a nti-NK1.1 mAb accelerated the development of autoantibody production, whereas augmentation of NK activity by administration of poly(I:C) inh ibited the development of autoantibody production. This inhibitory eff ect of poly(I:C) was abolished by prior depletion of NK cells. Interes tingly, suppression of autoantibody production was seen only when poly (I:C) was administrated within 1 week after injection of parental SC. Last, we demonstrate that adoptive transfer of interleukin-2 (IL-2)-ac tivated NK cells had a protective effect against the development of au toantibody production. These findings imply that NK cells may have a p rotective role in lupus-like disease especially in its early stage. In addition, it opens up the possibility that adoptive immunotherapy wit h IL-a-activated NK cells can delay or even prevent the development of autoimmune disease. (C) 1995 Academic Press, Inc.