RESUMO
The induction of monocyte IL-1 mRNA during T cell activation requires that monocytes receive contact-dependent signals from activated T cells. Furthermore, the ability of T cells to induce IL-1 beta mRNA is not constitutive but rather is rapidly acquired (< or = 30 min) following activation via mechanisms that do not require protein synthesis. The goal of these studies is to identify the T cell signal(s) that mediates the cell contact-dependent induction of monocyte IL-1 beta mRNA. The induction of IL-1 beta mRNA during anti-CD3 mitogenesis was significantly inhibited by anti-CD2 mAb, whereas mAb against CD11a, CD18, CD69, or CD5 molecules had no effect. The inhibition of IL-1 beta mRNA induction by anti-CD2 mAb was restricted to only those mAb that block CD2/CD58(LFA-3) interactions. Furthermore, anti-CD2 blocked the induction of monocyte IL-1 beta mRNA by T cells that were preactivated using either immobilized anti-CD3 or anti-T11(2) plus anti-T11(3) mAb, thereby indicating that the inhibition of IL-1 beta mRNA was not due to negative signaling effects exerted on the T cell by anti-CD2. Finally, although anti-CD69 mAb had no effect on IL-1 beta mRNA induction, it inhibited the generation of soluble IL-1 beta. The combination of anti-CD69 and anti-CD2 mAb exhibited greater inhibition of secreted IL-1 beta than either antibody alone. These results indicate that CD2 is required for T cell induction of IL-1 beta mRNA through interaction with LFA-3 on the monocyte and that the generation of soluble IL-1 beta is regulated by CD69.
