FAS CROSS-LINKING MIMICS THE INHIBITORY EFFECT OF ANTI-CD3 ON IL-3-INDUCED HISTAMINE AND CYTOKINE PRODUCTION BY MURINE MYELOID SPLEEN-CELL PRECURSORS

In the present study we investigated the effect of anti-CD3 stimulatio n on IL-3-induced histamine, IL-6, and IL-4 synthesis by murine hemato poietic precursor cells. These activities were strikingly decreased in splenocytes from mice that had received a single intravenous injectio n of 10 mu g of anti-CD3 monoclonal antibody (mAb) 24 hours previously . A similar inhibition occurred after 24-hour in vitro stimulation of normal spleen cells with 1 mu g/mL of anti-CD3 mAb. In both situations the inhibitory effect depended on T cell activation in that treatment with F(ab')(2) fragments of anti-CD3 did not diminish secretion of hi stamine and cytokines. Cross-linking of Fas antigen on spleen cells mi micked the action of anti-CD3, provided that interferon (IFN)-gamma wa s present during the incubation period. Substantial amounts of this cy tokine were detected in spleen cell supernatants, which were able to r eplace recombinant IFN-gamma during Fas receptor cross-linking. This e ffect was entirely mediated by IFN-gamma, as assessed by its neutraliz ation in the presence of anti-IFN-gamma mAbs. In contrast to splenocyt es, bone marrow cells responded normally to IL-3 after in vivo or in v itro stimulation with anti-CD3. They were also not affected by combine d treatment with anti-Fas mAb and IFN-gamma. Together, our data suppor t the notion that the decrease in IL-3-induced histamine and IL-6 prod uction by splenocytes pretreated with anti-CD3 is mediated, at least i n part, by Fas/FasL interactions, suggesting that the activity of extr amedullary myeloid precursor cells can be modulated by molecules invol ved in apoptosis.