Secretion of bioactive interleukin-1 beta by dendritic cells is modulated by interaction with antigen specific T cells

The role of interleukin-1 beta (IL-1 beta) as a regulator of the immune res ponse, although extensively investigated, is still debated. We then studied the expression of IL-1 beta by human dendritic cells (DCs), the profession al antigen presenting cells, and its modulation during immune reactions in vitro. Our results show that, on maturation or tetanus toroid presentation to specific CD4(+) CD40L(+) T lymphocytes, DCs begin to accumulate IL-1 bet a precursor (pro-IL-1 beta) but do not secrete bioactive IL-1 beta, In cont rast, interaction with alloreactive T cells results in both stimulation of pro-IL-1 beta synthesis and secretion of processed isoforms of the cytokine , that display biologic activity. Both CD4(+) and CD8(+) subsets of allospe cific T lymphocytes are required: CD4(+) T cells drive the synthesis of pro -IL-1 beta through CD40 engagement but have no effects on pro-IL-1 beta pro cessing; CD8(+) T cells, unable to induce synthesis of pro-IL-1 beta per se , are responsible for the generation of mature IL-1 beta by pro-IL-1 beta-p roducing DCs, Interleukin-1 beta-converting enzyme (ICE) inhibitors do not prevent the recovery of IL-1 beta bioactivity after allorecognition, indica ting that allospecific CD8(+) T cells may induce the release of bioactive I L-1 beta via mechanism(s) other than ICE activation. Altogether, these find ings suggest that CD4(+) and CD8(+) T-lymphocyte subsets have distinct role s in the induction of IL-1 beta secretion by DCs and support the hypothesis that IL-1 beta plays a role in cell-mediated immune responses. (C) 2000 by The American Society of Hematology.