Signal delivery by physical interaction and soluble factors from accessory cells in the induction of receptor-mediated T-cell proliferation. Synergistic effect of BSF-2/IL-6 and IL-1.

Our recent study revealed that soluble factors derived from accessory cells (AC; monocytes) and physical interaction with T cells of the accessory cells are both required for the induction of the proliferation of human peripheral blood T cells by anti-CD3 antibody coupled on latex beads. The accessory cell-derived soluble factor could be replaced by IL-1 and IL-6, and the role of live macrophages for physical interaction with T cells was found to be replaceable with paraformaldehyde(PFA)-fixed macrophages, provided the macrophages were pretreated with interferon-gamma (IFN-gamma) before fixation. Quantitative analysis in the present study revealed that IL-1 and IL-6 act synergistically to induce T-cell proliferation in the above system but either one of the factors alone reveals only a marginal or weak activity. Furthermore, it was shown that the potentiating activity of the culture supernatants of monocytes was substantially inhibited by anti-IL-6 antibody. Taken together with our previous results that anti-IL-1 serum strongly inhibited the potentiating activity of the culture supernatant, these results indicate that the main responsible molecules in the culture supernatant are IL-1 and IL-6, although a presence of other effective factors is not excluded. The anti-CD3-induced thymidine uptake by T cells in the presence of IL-1 and IL-6 was significantly inhibited by anti-Tac antibody, suggesting that the proliferation of T cells in this system is mostly mediated by a IL-2-dependent pathway. Our study further showed that accessory cells seem to acquire cell surface properties necessary for the effective interaction with T cells during 6-24 hr of culture with IFN-gamma. Presumably, a certain molecule(s) required for the interaction is induced on the cell surface of the AC by IFN-gamma.