Expression and function of the IL-2 receptor in activated human plasmacytoid dendritic cells

Human and mouse plasmacytoid dendritic cells (PDC) express IL-2 mRNA specifically upon TLR stimulation, but not under CD40L stimulation. Even though the expression of the IL-2R by PDC has been described, the functional implications of this expression remain unknown. Here, we investigated the expression and function of the IL-2R in activated human PDC. The IL-2Ralpha chain, CD25, is expressed in both CpG- and CD40L-activated PDC. CD25 expression is a relatively rapid event, as the receptor was detected 6 h after the initial activation signal. Exogenous IL-2 added to CD40L-activated PDC increased the expression of CD25, enhanced the secretion of pro-inflammatory cytokines and promotes PDC survival. CpG-activated PDC cultured in the presence of IL-2R-blocking monoclonal antibodies showed a reduced expression of pro-inflammatory cytokines, especially TNF-alpha. This reduction was dose and time dependent, suggesting a regulatory role of IL-2 in TNF secretion that might occur at the post-transcriptional level. These results indicate that the expression of the IL-2R is relevant to human PDC activation, and that IL-2 may be an important auto- and/or paracrine factor modulating the activation and survival of PDC. Finally, CD25 expression may be considered as a useful early activation marker for human PDC.