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Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3809-3815
Secretion of bioactive interleukin-1 by dendritic cells is
modulated by interaction with antigen specific T cells
Stefania Gardella,
Cristina Andrei,
Sara Costigliolo,
Lucia Olcese,
M. Raffaella Zocchi, and
Anna Rubartelli
From the National Institute for Cancer Research, Genova, and the
Laboratory of Tumor Immunology, Scientific Institute San Raffaele,
Milano, Italy.
The role of interleukin-1 (IL-1) as a regulator of the immune
response, although extensively investigated, is still debated. We then
studied the expression of IL-1 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-1 precursor (pro-IL-1) but do not secrete bioactive IL-1. In contrast, interaction with alloreactive T cells results in both stimulation of pro-IL-1 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-1 through
CD40 engagement but have no effects on pro-IL-1 processing;
CD8+ T cells, unable to induce synthesis of pro-IL-1
per se, are responsible for the generation of mature IL-1 by
pro-IL-1-producing DCs. Interleukin-1-converting enzyme (ICE)
inhibitors do not prevent the recovery of IL-1 bioactivity after
allorecognition, indicating that allospecific CD8+ T
cells may induce the release of bioactive IL-1 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-1 secretion by DCs and support
the hypothesis that IL-1 plays a role in cell-mediated immune responses.
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