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

• Published in: Blood Vol. 95; no. 12; pp. 3809 - 3815
• Main Authors: GARDELLA, S, ANDREI, C, COSTIGLIOLO, S, OLCESE, L, ZOCCHI, M. R, RUBARTELLI, A
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15.06.2000
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Modulation of the immune response (stimulation, suppression); Human; Dendritic cell; Immune response; Leukocyte; Secretion; Cytokine; Accessory cell; Helper cell; Interleukin 1β; Cell subpopulation; Regulation(control); T-Lymphocyte; Suppressive cell
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v95.12.3809

Abstract The role of interleukin-1β (IL-1β) as a regulator of the immune response, although extensively investigated, is still debated. We then studied the expression of IL-1β 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-1β precursor (pro–IL-1β) but do not secrete bioactive IL-1β. In contrast, interaction with alloreactive T cells results in both stimulation of pro–IL-1β 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-1β through CD40 engagement but have no effects on pro–IL-1β processing; CD8+ T cells, unable to induce synthesis of pro–IL-1β per se, are responsible for the generation of mature IL-1β by pro–IL-1β–producing DCs. Interleukin-1β–converting enzyme (ICE) inhibitors do not prevent the recovery of IL-1β bioactivity after allorecognition, indicating that allospecific CD8+ T cells may induce the release of bioactive IL-1β 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-1β secretion by DCs and support the hypothesis that IL-1β plays a role in cell-mediated immune responses.