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

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Abstract
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 IL 2 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 IL 3 and interferon-γ (IFN-γ) in primary cultures. No IL 4 was demonstrable irrespective of the type of presenting cells used, and both tissue macrophages and dendritic cells can induce synthesis of IL 6. Likewise, in secondary alloresponses both dendritic cells and to a lesser extent tissue macrophages induce release of IL 3, no IL 4 is detectable, and activated macrophages and B cells raise IFN-γ 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) IL 4 was now detectable in the supernatants but only where dendritic cells had been used as APC, and (b) both resting and activated macrophages induced IL 2 and IFN-γ. By the eighth cycle of allostimulation there is negligible IL 2. Dendritic cells, tissue macrophages and activated B cells constitute a hierarchy of APC for IL 3, IFN-γ and IL 4. These findings therefore demonstrate the role of dendritic cells as potent in vitro inducers of IL 3, IL 4 and IFN-γ synthesis as well as of IL 2.