T Lymphocytes Potentiate Murine Dendritic Cells to Produce IL-12

IL-12 is mainly produced by CD8alpha(+) dendritic cells (DCs) and induces Th1 polarization of the immune response. We investigated the influence of lymphocytes on splenic DC (SDC) and thymic DC (TDC) development and on their IL-12 production capacity. First, CD3epsilon(-/-) mice, lacking T cells, and RAG-2(-/-) mice, lacking T and B cells, possess numbers of SDCs, TDCs, and CD8alpha(+) SDCs similar to wild-type (WT) mice. Second, SDCs and TDCs from CD3epsilon(-/-) mice do not secrete IL-12 in vitro after different stimulations, whereas DCs from pTalpha(-/-) mice, possessing reduced T cell number, and RAG-2(-/-) mice, produce an IL-12 level similar to that of WT DCs. We show that T lymphocytes restore the capacity of DCs to produce IL-12 after stimulation in vivo by reconstitution of CD3epsilon(-/-) mice with WT T cells and in vitro by coculture of CD3epsilon(-/-) DCs with WT T cells. The regulation of IL-12 production occurred at the transcriptional level, with an increase of IL-12p35 transcripts and a decrease of IL-12p40 transcripts. Although IL-4 restores IL-12 production by CD3epsilon(-/-) SDCs, anti-IL-4 Abs inhibited only partially the IL-12 production in coculture of CD3epsilon(-/-) DCs and WT T cells. Taken together, these data show that T lymphocytes potentiate IL-12 production by DCs and that IL-4 is not solely involved in this regulation. In conclusion, B and T cells exert balanced actions on DCs by respectively inhibiting or promoting IL-12 production.