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

Abstract

SUMMARYIL-12 is the prominent inducer of Th1 responses in humans and in the mouse. CD40 ligand (CD40L) plays important roles in regulation of immune responses, including T cell-dependent activation of B cells and cytokine production by monocytes and dendritic cells. The present study examined the in¯uences of IL-12 on the CD40L expression of activated human CD4T cells. IL-12 enhanced CD40L expression on CD4T cells stimulated with immobilized anti-CD3 in the complete absence of accessory cells, whereas IL-4 and IL-10 decreased it. Exogenous interferon-gamma (IFN-g) did not increase CD40L expression on immobilized anti-CD3 stimulated CD4T cells at any time up to 168 h of culture. The IL-12-induced enhancement of CD40L expression on anti-CD3 activated CD4T cells was not in¯uenced in the presence of a metalloproteinase inhibitor KB8301, which up-regulated CD40L expression by preventing the processing of membrane-bound CD40L, or B cells, which down-regulated CD40L expression by receptor-mediated endocytosis. These results indicate that IL-12 enhances the CD40L expression of activated CD4T cells independently of the IFN-g production. The data thus suggest that Th1 responses induced by IL-12 might play an important role in the regulation of humoral immune responses through up-regulated CD40L expression.

Anti-CD40 Antibody Induces Antitumor and Antimetastatic Effects: The Role of NK Cells

“…It has been shown that NK cells express CD40L (26) and can be activated to kill CD40-expressing tumors in vitro (26). Therefore, it is possible that increased production of IL-12 by activated APC can up-regulate expression of CD40L on NK cells in a similar way as was reported for CD4 ϩ T cells (29). Consequently, those activated NK cells may kill tumor cells via CD40-CD40L interaction.…”

Differential effects of IFN-α on the expression of various TH2 cytokines in human CD4+ T cells

“…21 T cells were obtained from the treated cell population by rosetting with neuraminidasetreated sheep red blood cells, as previously described. 22 Purified CD4 1 T cells were further prepared by means of positive selection with anti-CD4 microbeads and MACS (Miltenyi Biotec, Auburn, Calif). The CD4 1 T-cell population obtained in this manner contained less than 0.1% esterase-positive cells, less than 0.1% NK cells, less than 0.1% CD19 1 cells, and greater than 96% CD4 1 T cells.…”

Suppression of Innate Immune Cytokines and Interferon Regulatory Factor-1 by Endogenous Interferon-Alpha in Response to Respiratory Syncytial Virus in Neonate Mononuclear Cells

“…It is known that IL-12 and/or IL-18 enhance the expression of IFN-γ in adult MCs (Hirohata, 1999;Mbawuike et al, 1999;Puren et al, 1998). This led us to conclude that live RSV stimulates IFN-α production, which in turn induces suppression of innate cytokine responses in neonate MCs.…”