[Mechanism of suppression of colchicine in experimental allergic encephalomyelitis].
Experimental allergic encephalomyelitis(EAE) has been used as an animal model of multiple sclerosis. The establishment of an adoptive transfer system employing encephalitogenic T-cells simplifies the analysis of the pathogenesis of this demyelinating disease. Colchicine, a drug used for gout, has recently been shown to be effective in the treatment of various autoimmune diseases including multiple sclerosis. Moreover, it has been shown that the drug suppresses the development of EAE in SJL mice in vivo. The precise mechanism of this suppression, however, remains unknown. Bearing this in mind, we have attempted to clarify this phenomenon using an adoptive transfer system with encephalitogenic T-cell lines. Lymphocytes from the SJL mice, which had been immunized with bovine myelin basic protein(MBP) and complete Freund's adjuvant were cultured for 4 days with MBP. Following this, the lymphocytes were subcultured in medium containing Con A supernatant(CAS) without antigen. The cells were then stimulated with MBP for 4 days in the presence of antigen presenting cells(APC). Cells were maintained by alternate antigenic stimulation without CAS and propagation in CAS medium over 90 days. The established cell lines were shown to have the cell surface markers of ly-1+, L3t4+, Ly-2-, which are characteristic of T helper/inducer cells. The syngeneic mice receiving these T-cells via tail veins developed neurological deficits in 2 weeks, and inflammatory demyelination was observed in the diseased animals, indicating that the T-cell lines did have encephalitogenicity. Colchicine treatment of the mixture of APC and T-cells in vitro suppressed the proliferation of T-cells, and this was dose dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003078:Colchicine / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D004676:Myelin Basic Protein; D003078:Colchicine