DENDRITIC CELLS PRODUCE IL-12 AND DIRECT THE DEVELOPMENT OF TH1 CELLSFROM NAIVE CD4(-CELLS() T)

Dendritic cells are APCs that are unique in their potency to stimulate proliferation of primary Ag-specific responses in vitro and in vivo. in this study, we demonstrate that dendritic cells can produce IL-12, a dominant cytokine involved in the development of IFN-gamma-producing T cells. This finding resulted from our observations that dendritic c ell-induced Th1 development from total CD4(+) T cells upon neutralizat ion of endogenous levels of IL-4 was IL-12-dependent. Furthermore, we demonstrate that dendritic cells can induce the development of Th1 cel ls from Ag-specific naive LECAM-1(bright) CD4(+) T cells obtained from alpha beta-TCR transgenic mice, provided that CD4(+) LECAM-1(dull) T cells, which produce significant levels of IL-4, are not present in th e primary cultures. Production of IL-12 by dendritic cells was confirm ed by positive immunofluoresence staining with Abs specific for the in ducible IL-12 p40 subunit. This suggests that in addition to inducing proliferation and clonal expansion of naive T cells, dendritic cells, by their production of IL-12, play a direct role in the development of IFN-gamma-producing cells that are important for cell-mediated immune responses.