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

The role of interleukin-1beta (IL-1beta) as a regulator of the immune response, although extensively investigated, is still debated. We then studied the expression of IL-1beta by human dendritic cells (DCs), the professional antigen presenting cells, and its modulation during immune reactions in vitro. Our results show that, on maturation or tetanus toxoid presentation to specific CD4(+) CD40L(+) T lymphocytes, DCs begin to accumulate IL-1beta precursor (pro-IL-1beta) but do not secrete bioactive IL-1beta. In contrast, interaction with alloreactive T cells results in both stimulation of pro-IL-1beta synthesis and secretion of processed isoforms of the cytokine, that display biologic activity. Both CD4(+) and CD8(+) subsets of allospecific T lymphocytes are required: CD4(+) T cells drive the synthesis of pro-IL-1beta through CD40 engagement but have no effects on pro-IL-1beta processing; CD8(+) T cells, unable to induce synthesis of pro-IL-1beta per se, are responsible for the generation of mature IL-1beta by pro-IL-1beta-producing DCs. Interleukin-1beta-converting enzyme (ICE) inhibitors do not prevent the recovery of IL-1beta bioactivity after allorecognition, indicating that allospecific CD8(+) T cells may induce the release of bioactive IL-1beta via mechanism(s) other than ICE activation. Altogether, these findings suggest that CD4(+) and CD8(+) T-lymphocyte subsets have distinct roles in the induction of IL-1beta secretion by DCs and support the hypothesis that IL-1beta plays a role in cell-mediated immune responses. (Blood. 2000;95:3809-3815)