Sensitized lymphocytes and CD40 ligation augment interleukin-12 productionby human dendritic cells in response to Toxoplasma gondii

Dendritic cells (DC) are potent antigen-presenting cells that can stimulate T cell responses by secreting cytokines. During Toxoplasma gondii infectio n, host immunity is mediated by interferon-gamma, which is induced by inter leukin-12 (IL-12). Whether T. gondii infection would stimulate human DC to produce IL-12 was determined. DC were generated from human peripheral blood mononuclear cells cultured with recombinant human granulocyte-macrophage c olony-stimulating factor and recombinant human IL-4. DC secreted high level s of IL-12 in response to lipopolysaccharide but not to either live T. gond ii tachyzoites or soluble antigen. However, IL-12 production in response to T. gondii was observed when DC were cocultured in contact with lymphocytes isolated from seropositive donors. Ligation of CD40: CD154 was partially e ssential for IL-12 secretion. These data demonstrate that signals obtained from contact with sensitized lymphocytes are critical for human DC to secre te IL-12 in response to T. gondii.