CD40L‐Induced IL‐12 Production is Further Enhanced by the Th2 Cytokines IL‐4 and IL‐13

• Published in: Scandinavian journal of immunology Vol. 53; no. 5; pp. 455 - 463
• Main Authors: Bullens, D. M. A., Kasran, A., Thielemans, K., Bakkus, M., Ceuppens, J. L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.2001; Wiley Subscription Services, Inc
• Subjects: Autocrine Communication; B-Lymphocytes - immunology; CD40 antigen; CD40 Ligand - immunology; CD40L protein; Cells, Cultured; Drug Synergism; Female; Humans; Interleukin-10 - immunology; Interleukin-12 - biosynthesis; Interleukin-12 - genetics; Interleukin-13 - pharmacology; Interleukin-4 - pharmacology; Male; Monocytes - immunology; RNA, Messenger - biosynthesis; Th2 Cells - immunology; Time Factors; Tumor Necrosis Factor-alpha - biosynthesis; Up-Regulation
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1046/j.1365-3083.2001.00900.x

Interaction of the CD40L (CD154) molecule on activated T cells with its receptor, CD40, on macrophages and dendritic cells (DC) provides a strong signal for interleukin (IL)‐12 production. As IL‐12 is the most important factor in driving Th precursor (Thp) cells into T(h)elper 1 cells, CD40–CD40L interactions strongly promote Th1 differentiation. Th2 cytokines (IL‐4, IL‐13, IL‐10) on the other hand, are known to inhibit Th1 differentiation, and to promote either directly or indirectly, Th2 differentiation. Inhibition of lipopolysaccharide (LPS)‐induced IL‐12 production by IL‐4, IL‐13 and IL‐10 is supposed to be one such mechanism. However, we here report that IL‐4 and IL‐13 enhance p70 IL‐12 production and p40 mRNA transcription by human monocytes when the latter are stimulated trough triggering of CD40. This effect on IL‐12 induction is most clear in the presence of interferon (IFN)‐γ, which upregulates CD40 expression. IL‐10 potently inhibits IL‐12 production. The increased IL‐12 production in the presence of IL‐4 and IL‐13 is however, not the indirect result of a reduction in IL‐10 production, but is most likely owing to a direct effect of IL‐4 and IL‐13. We conclude that IL‐4 and IL‐13 enhance rather than decrease the IL‐12 production by human monocytes during interaction with T cells. This effect can potentially contribute in vivo to switching of an ongoing Th2 response towards a Th1 response and the findings also support the dominant effect of CD40/CD40L interaction on Th1 development, even in the presence of Th2 cytokines.