Dendritic cells (DCs) express functional purinergic receptors, but the effects of purine nucleotides on DCs functions have been only marginally investigated. Here we report the ability of ATP to affect the maturation and antigen presenting function of monocyte-derived DCs in vitro. Chronic stimulation of DCs with low, non cytotoxic ATP doses, but not with UTP, increased membrane expression of CD54, CD80, CD86 and CD83 as well as their capacity of inducing T lymphocyte proliferation in the primary mixed leukocyte reaction assay. Moreover, ATP enhanced LPS- or sCD40L-induced DC membrane maturation. On the other hand, ATP markedly and dose-dependently inhibited the production of TNF-alpha, IL-6 and IL-12 by LPS-stimulated DCs. In contrast, IL-10 production was only slightly affected. These effects did not require ATP metabolism as they were shared by the poorly hydrolyzable ATP analog ATP-gamma-S and were not prevented by specific inhibitors of the adenosine receptors. In addition, ATP activity was not blocked by treating DCs with indomethacin, suggesting that it was not mediated by prostaglandins. More interesting, T cell lines generated from allogeneic naive CD45RA+ T cells with DCs matured in the presence of ATP, produced lower amounts of IFN-gamma and higher levels of IL-4, IL-5 and IL-10. Addition of IL-12 and/or anti-IL-10 mAb restored IFN-gamma production, and reduced IL-4, IL-5 and IL-10 release. The results indicate that chronic stimulation with ATP, although induces phenotypic maturation, can potently inhibit the ability of maturing DCs to initiate Th1 responses.
Adenosine triphosphate (ATP) induces a distorted maturation of dendritic cells and inhibits their capacity to initiate TH1 responses.
FERRARI, Davide;DI VIRGILIO, Francesco;
2001
Abstract
Dendritic cells (DCs) express functional purinergic receptors, but the effects of purine nucleotides on DCs functions have been only marginally investigated. Here we report the ability of ATP to affect the maturation and antigen presenting function of monocyte-derived DCs in vitro. Chronic stimulation of DCs with low, non cytotoxic ATP doses, but not with UTP, increased membrane expression of CD54, CD80, CD86 and CD83 as well as their capacity of inducing T lymphocyte proliferation in the primary mixed leukocyte reaction assay. Moreover, ATP enhanced LPS- or sCD40L-induced DC membrane maturation. On the other hand, ATP markedly and dose-dependently inhibited the production of TNF-alpha, IL-6 and IL-12 by LPS-stimulated DCs. In contrast, IL-10 production was only slightly affected. These effects did not require ATP metabolism as they were shared by the poorly hydrolyzable ATP analog ATP-gamma-S and were not prevented by specific inhibitors of the adenosine receptors. In addition, ATP activity was not blocked by treating DCs with indomethacin, suggesting that it was not mediated by prostaglandins. More interesting, T cell lines generated from allogeneic naive CD45RA+ T cells with DCs matured in the presence of ATP, produced lower amounts of IFN-gamma and higher levels of IL-4, IL-5 and IL-10. Addition of IL-12 and/or anti-IL-10 mAb restored IFN-gamma production, and reduced IL-4, IL-5 and IL-10 release. The results indicate that chronic stimulation with ATP, although induces phenotypic maturation, can potently inhibit the ability of maturing DCs to initiate Th1 responses.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
