Increased il-12 production in multiple sclerosis is mediated by activated t cells via cd40 ligand

K. E. Balashov, S. J. Khoury, P. A. Hafler, H. L. Weiner

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system postulated to be a Thl-type cell-mediated autoimmune disease. IFN-g administration has been shown to induce exacerbations of disease. We have previously found an increase in IFN-g production by anti-CD3 stimulated PBMC in progressive MS which was linked to endogenous IL-12 secretion. We investigated the mechanism of increased IL-12 secretion in MS. IL-12, a key cytokine in the development of Thl-type responses, is secreted by different populations of APCs but not by T cells. Staphylococcus aureus - induced IL-12 secretion was normal in MS but production of biologically active IL-12 p75 by anti-CD3 activated PBMC was increased in progressive MS vs. controls (20.9 ± 6.5 pg/ml vs. 1.4 ±1.1 pg/ml, p < 0.01). In experiments with separated PBMC populations, activated T cells were required for IL-12 production by APCs. Furthermore, anti-CD3 stimulated T cells from MS patients (but not controls) induced IL-12 production by APCs from both MS patients and controls. Both activated CD4+ and CD8+ T cells from MS patients were effective in the induction of IL-12 production by APCs. Experiments with neutralizing mAb showed that CD40-ligand expressed by activated T cells was required for induction of IL-12 secretion by APCs. We conclude that activated T cells are responsible for elevated IL-12 production by APCs in progressive MS and contribute to abnormal Thl responses in the disease.

Original languageEnglish (US)
Pages (from-to)A1307
JournalFASEB Journal
Issue number6
StatePublished - 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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