Human Th1 responses driven by IL-12 are associated with enhanced expression of CD40 ligand

IL-12 is the prominent inducer of Th1 responses in humans and in the mouse. CD40 ligand (CD40L) plays important roles in regulation of immune response s, including T cell-dependent activation of B cells and cytokine production by monocytes and dendritic cells. The present study examined the influence s of IL-12 on the CD40L expression of activated human CD4(+) T cells. IL-12 enhanced CD40L expression on CD4(+) T cells stimulated with immobilized an ti-CD3 in the complete absence of accessory cells, whereas IL-4 and IL-10 d ecreased it. Exogenous interferon-gamma (IFN-gamma) did not increase CD40L expression on immobilized anti-CD3 stimulated CD4(+) T cells at any time up to 168 h of culture. The IL-12-induced enhancement of CD40L expression on anti-CD3 activated CD4(+) T cells was not influenced in the presence of a m etalloproteinase inhibitor KB8301, which up-regulated CD40L expression by p reventing the processing of membrane-bound CD40L, or B cells, which down-re gulated CD40L expression by receptor-mediated endocytosis. These results in dicate that IL-12 enhances the CD40L expression of activated CD4(+) T cells independently of the IFN-gamma production. The data thus suggest that Th1 responses induced by IL-12 might play an important role in the regulation o f humoral immune responses through up-regulated CD40L expression.