Interleukin‐18 synthesis and secretion by dendritic cells are modulated by interaction with antigen‐specific T cells

We show that interleukin‐18 is constitutively produced by dendritic cells; synthesis and secretion are poorly affected by maturative stimuli. Challenge of dendritic cells with autologous antitetanus toxoid T lymphocytes results in a secretory switch, with induction of secretion of biologically active interleukin‐18 and decrease of its intracellular content. Similarly, when dendritic cells are challenged with allospecific T cells a dramatic decrease of intracellular interleukin‐18 content occurs, whereas no effects are observed after co‐culture with autologous activated T cells. The induction of secretion can be mediated by engagement of CD40 on dendritic cells, as indicated by the increased amount of interleukin‐18 in dendritic cell supernatants after CD40 triggering by anti‐CD40 antibodies. However, CD40 engagement, unlike from antigen‐specific T cells, does not result in reduced intracellular interleukin‐18 content, suggesting that this decrease may be mediated by structure(s) involved in antigen recognition. J. Leukoc. Biol. 66: 237–241; 1999.