Effect of Adenosine Diphosphate on Dendritic Cell and T Cell Responses

Abstract

Nucleotides, such as ATP and its derivatives, are released at high concentrations at sites of inflammation and modulate the immune response. When cultured in the presence of ADP or stable analogue ADP?S, DC surface expression of MHC-II and co-stimulatory molecules, CD40 and CD86 was unchanged. When DCs were pre-treated with ADP or ADP?S, there was no change in their ability to activate naïve CD4+ T cells. However, when CD4+ T cells were activated in the presence of ADP or ADP?S, activation and proliferation were significantly decreased. This correlated with a significant reduction in IL-2 secretion and CD25 surface expression, which may be due to decreased ERK and Akt phosphorylation. CD8+ T cell proliferation was unaffected by the addition of ADP or ADP?S, but secretion of IFN-? was significantly reduced. By demonstrating that ADP inhibits CD4+ T cell responses, we have identified a potential target of immune modulation by clinical intervention.