Increased interleukin 12 production in progressive multiple sclerosis: Induction by activated CD4+T cells via CD40 ligand

• DOI: 10.1073/pnas.94.2.599
• Publication Date: 2002-07-26T14:32:33Z
• Authors: Konstantin E. Bal...; Derek R. Smith; Samia J. Khoury; David A. Hafler; Howard L. Weiner
• Keywords: Pathogenesis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system postulated to be cell-mediated autoimmune in which interferon γ (IFN-γ) plays an important role. There increased IFN-γ secretion MS, and administration induces exacerbations disease. We found that interleukin 12 (IL-12) was responsible for raised MS as anti-IL-12 antibodies reversed anti-CD3-induced patients normal levels. Furthermore, we marked increase T cell receptor-mediated IL-12 progressive vs. controls (24.8 ± 7.7 pg/ml 1.5 1.0 pg/ml, P = 0.003) relapsing–remitting (3.7 1.4 < 0.05). Investigation cellular basis demonstrated cells from induced non-T cells, could even drive subjects produce IL-12. Anti-CD40 ligand antibody completely blocked by activated CD40 expression CD4 + controls. The ligand-dependent Th1-type immune activation observed but not form suggesting link pathogenesis progression providing intervention