Antigen-activated T cells induce IL-12p75 production from dendritic cells in an IFN-?-independent manner.

ABSTRACT: The addition of IL-12p75 to naïve CD4(+) T cells promotes their differentiation towards a TH1-type cytokine pattern. Dendritic cells stimulated by LPS generate IL-12p75, but only if the environment also contains IFN-?. Thus, it appears that IFN-? is needed to start the response that will result in further production of IFN-?. We previously reported that paradoxically DCs produce IL-12p75 only after engaging primed, but not naïve T cells. This study examines the mechanism by which primed T cells trigger IL-12p75 secretion and asks whether this induction is also dependent on the presence of IFN-?. Here, we show that, in contrast to LPS, primed T cells induce IL-12p75 in an IFN-?-independent manner. Addition of rIFN-? to cocultures of naïve T cells with DCs did not induce IL-12p75. Moreover, antigen-activated CD4(+) T cells from wild type or IFN-?-deficient mice both initiated IL-12p75 production from DCs. Surprisingly, we found that synergies between three T-cell-derived factors - CD40 Ligand, IL-4 and GM-CSF - were necessary and sufficient for IL-12p75 production. These results suggest that there are at least two distinct pathways for IL-12p75 production in vivo. Furthermore, the T-cell-dependent pathway of IL-12p75 production employs molecules that are not classically associated with a TH1-type response.

SUBMITTER: Abdi K 

PROVIDER: S-EPMC3008555 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature