DECREASED CD3-MEDIATED INTERFERON-GAMMA PRODUCTION IN RELAPSING-REMITTING MULTIPLE-SCLEROSIS

Multiple sclerosis (MS) is a chronic inflammatory disease of the centr al nervous system that has been postulated to be T-cell mediated. We e xamined the proliferation and cytokine secretion of mononuclear cells after stimulation with OKT3 (anti-CD3) monoclonal antibody concanavali n A, or ionomycin plus myristic acid palmityl ester in subjects with s table relapsing-remitting MS. Control subjects demonstrated good proli feration to anti-CD3 monoclonal antibody whereas subjects with relapsi ng-remitting MS showed a significantly decreased anti-CD3 monoclonal a ntibody-mediated response. There was no difference in concanavalin or ionomycin plus myristic acid palmityl ester stimulation between contro l subjects and MS subjects. Secretion of interferon-gamma was signific antly decreased and transforming growth factor-beta was significantly increased from cultures stimulated with anti-CD3 monoclonal antibody, but not ionomycin plus myristic acid palmityl ester or concanavalin A, in MS patients compared to control subjects. Secretion of interleukin -10 and tumor necrosis factor-alpha was not different between control subjects and MS patients following stimulation with anti-CD3 monoclona l antibody, concanavalin A, or ionomycin plus myristic acid palmityl e ster, or of interleukin-2 and interleukin-4 following stimulation with anti-CD3 monoclonal antibody or concanavalin A. An abnormality of sig nal transduction and secretion of the immuno-modulatory molecule inter feron-gamma may exist in MS via the CD3 T-cell receptor complex.