Antigen presentation by dendritic cells provides optimal stimulation for the production of interleukin (IL) 2, IL 4 and interferon-gamma by allogeneic T cells.

Previous studies have shown that dendritic cells are the most potent inducers of T cell proliferation in vitro and that this is reflected in the release of interleukin (IL) 2 into culture supernatants during dendritic cell-T cell interaction. However, the role of the dendritic cells, and, indeed, of the antigen-presenting step, has not yet been explored with respect to other T cell-derived cytokines, in either a qualitative or relative fashion. In this study, therefore, we have examined the comparative role of different antigen-presenting cells (APC) as inducers of T cell cytokine release in allogeneic responses. We have confirmed that dendritic cells are the most effective inducers for IL2 and have shown that this is true not only in primary alloresponses, but also in alloresponder T cells maintained for extended periods and then rechallenged. Dendritic cells were also the most potent inducers of IL3 and interferon-gamma (IFN-gamma) in primary cultures. No IL4 was demonstrable irrespective of the type of presenting cells used, and both tissue macrophages and dendritic cells can induce synthesis of IL6. Likewise, in secondary alloresponses both dendritic cells and to a lesser extent tissue macrophages induce release of IL3, no IL4 is detectable, and activated macrophages and B cells raise IFN-gamma levels in the supernatants albeit to a lower concentration than that seen when dendritic cells are used as stimulators. The results were similar in the tertiary alloresponse except that (a) IL4 was now detectable in the supernatants but only where dendritic cells had been used as APC, and (b) both resting and activated macrophages induced IL2 and IFN-gamma. By the eighth cycle of allostimulation there is negligible IL2. Dendritic cells, tissue macrophages and activated B cells constitute a hierarchy of APC for IL3, IFN-gamma and IL4. These findings therefore demonstrate the role of dendritic cells as potent in vitro inducers of IL3, IL4 and IFN-gamma synthesis as well as of IL2.