CD8 T cell mediated induction of interleukin-12p70 production by dendritic cells

Abstract

In this study, we set up an in vitro system to study the effects of CD8 T cells on splenic DC IL-12p70 production during an antigen specific interaction. We find that mouse splenic DCs respond to CD8 T cells with IL-12p70 production only when DCs were concurrently stimulated with TLR ligands. Different TLR ligands cooperated with CD8 T cells for IL-12p70 production to different extents. In particular, CpG was most effective for the induction of IL-12p70, while other TLR ligands, like LPS, were only moderately effective. We also found the immune status of the CD8 T cells was important for priming DCs for IL-12p70 production. Pre-activation of CD8 T cells was required for effective DC IL-12p70 priming with LPS. With CpG, naturally occurring memory CD8 T cells were superior to naC/ve CD8 T cells for the induction of IL-12p70. Furthermore, we also show that apart from IFN-N3, CD8 T cells also use CD40L, GM-CSF and TNF-N1 to prime DCs for IL-12p70 production. Of the splenic DC subsets, CD8N1+ DCs were the primary source of IL-12p70, demonstrating the specialized role of the CD8N1+ DC subset in this process. Interestingly, CD8N1+ DCs are also implicated as the principle DC subset for cross-presentation and cross-priming cytotoxic CD8 T cell responses. Our study describes a novel pathway for the induction effective IL-12p70 responses to cross-presented antigens.