Following direct CD40 activation, human primary microglial cells produce IL-12 p40 but not bioactive IL-12 p70

There is accumulating evidence that interleukin 12 (IL-12) is involved in t he pathogenesis of multiple sclerosis, In the periphery, this cytokine is p roduced by antigen-presenting cells (APCs) following interaction with activ ated T cells, CD40 ligation plays a crucial role in this production. Microg lial cells are thought to play a major role in antigen presentation in the central nervous system. In this work, we examined IL-12 production by human primary microglial cells after CD40 ligation, These cells expressed CD40 a nd MHC class II following interferon-gamma activation. IL-12 p40 mRNA and p rotein, but not bioactive IL-12 p70, were detected in response to direct CD 40 activation. Microglial cells co-cultured with activated allogenic CD4+ T lymphocytes also produced IL-12 p40 but not IL-12 p70, This IL-12 p40 prod uction was inhibited by anti-CD40 ligand, Altogether, these results suggest that CD40-CD40-ligand interaction provides a signal that triggers IL-12 p4 0 expression. However, other interaction(s) may be required during antigen presentation for bioactive heterodimeric IL-12 p70 to be produced by microg lial cells. (C) 2001 Academic Press.