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*
Laboratory of Immunology, Istituto Dermopatico dell’Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy; and
Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Ferrara, Italy
Dendritic cells (DCs) express functional purinergic receptors, but
the effects of purine nucleotides on DC functions have been marginally
investigated. In this study, we report on the ability of micromolar
concentrations of ATP to affect the maturation and Ag-presenting
function of monocyte-derived DCs in vitro. Chronic stimulation (24 h)
of DCs with low, noncytotoxic ATP doses increased membrane expression
of CD54, CD80, CD86, and CD83, slightly reduced the endocytic activity
of DCs, and augmented their capacity to promote proliferation of
allogeneic naive T lymphocytes. Moreover, ATP enhanced LPS- and soluble
CD40 ligand-induced CD54, CD86, and CD83 expression. On the other hand,
ATP markedly and dose-dependently inhibited LPS- and soluble CD40
ligand-dependent production of IL-1
, IL-1
, TNF-, IL-6, and
IL-12, whereas IL-1 receptor antagonist and IL-10 production was not
affected. As a result, T cell lines generated from allogeneic naive
CD45RA+ T cells primed with DCs matured in the presence of
ATP produced lower amounts of IFN-
and higher levels of IL-4, IL-5,
and IL-10 compared with T cell lines obtained with LPS-stimulated DCs.
ATP inhibition of TNF- and IL-12 production by mature DCs was not
mediated by PGs or elevation of intracellular cAMP and did not require
ATP degradation. The inability of UTP and the similar potency of ADP to
reproduce ATP effects indicated that ATP could function through the P2X
receptor family. These results suggest that extracellular ATP may serve
as an important regulatory signal to dampen IL-12 production by DCs and
thus prevent exaggerated and harmful immune
responses.
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