Mechanism of suppression of colchicine in experimental allergic encephalomyelitis
Tateyama, M.
Hokkaido Journal of Medical Science 63(1): 72-79
1988
ISSN/ISBN: 0367-6102 PMID: 2452125 Document Number: 310152
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 demeylinating disease. Colchicine, a drug usd 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 myelinbasic protein (MPB) 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. In addition APC and T-cells were heated separately, and assayed for the T-cell proliferation after mixing. APC treated with colchicine was shown to induce comparable T-cell proliferation to that induced by non-treated APC. Moreover, APC collected from the colchicine treated mice also induced proliferation of T cells. When the T-cells were incubated with colchicine, however, T-cell proliferation was suppressed in the presence of APC non-treated with colchicine (p < 0.05). Thus, it can be shown that colchicine may inhibit the proliferation of MBP primed T-cells in vitro without any influence on APC function, and that this inhibition is one of the mechanisms by which the drug suppresses the development of EAE.