RECRUITMENT OF HEPATIC NK CELLS BY IL-12 IS DEPENDENT ON IFN-GAMMA AND VCAM-1 AND IS RAPIDLY DOWN-REGULATED BY A MECHANISM INVOLVING T-CELLS AND EXPRESSION OF FAS

NK cells have been shown to be important antitumor or antiviral effect or cells in the liver. In the present study we have examined the facto rs that regulate the initial recruitment and subsequent fate of hepati c NK and T cells in mice treated with IL-12 or IL-2. Daily administrat ion of IL-12 caused a rapid initial increase in NK cells followed by a subsequent decrease that coincided with an accumulation of T cells, T he recruitment of hepatic Mt cells by IL-12, but not the subsequent T cell infiltrate, was abrogated in IFN-gamma(-/-) mice. In contrast, da ily administration of IL-2 caused a sustained increase in liver-associ ated NK cells that was not diminished in IFN-gamma(-/-) mice, The IL-1 2-induced recruitment in both hepatic NK and T cells was abrogated by in vivo treatment with anti-VCAM-1 mAbs, while treatment with anti-ICA M-1 Abs decreased only the recruitment of T cells in the IL-12-treated mice, The rapid loss of newly recruited hepatic NK cells in IL-12-tre ated mice did not occur in SCID mice or in B.MRL-Fas(lpr) (Fas(-)) and B6Smn.C3H-Fasl(gld) (FasL(-)) mutant mice, suggesting that T cells ca n actively eliminate hepatic Mt cells through a Fas-dependent mechanis m, These Endings also imply that during the endogenous innate immune r esponse to infectious agents or tumors or in the host response induced by cytokine therapies, the biologic effects of NK cells may be limite d by T cell-mediated effects.