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

Stefania Gardella, Cristina Andrei, Sara Costigliolo, Lucia Olcese, M. Raffaella Zocchi, Anna Rubartelli

Research output: Contribution to journalArticle

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. (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)3809-3815
Number of pages7
JournalBlood
Volume95
Issue number12
Publication statusPublished - Jun 15 2000

ASJC Scopus subject areas

  • Hematology

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    Gardella, S., Andrei, C., Costigliolo, S., Olcese, L., Zocchi, M. R., & Rubartelli, A. (2000). Secretion of bioactive interleukin-1β by dendritic cells is modulated by interaction with antigen specific T cells. Blood, 95(12), 3809-3815.