The Role Of Costimulatory Molecules In Experimental Autoimmune Encephalomyelitis And Effects Of Drug

Objective :To establish experimental autoimmune encephalomyelitis (EAE) models from C57BL/6 mice and to provide a basis for preliminary studying the immune and inflammatory mechanisms of costimulatory molecule (CD80/B7-1,CD86/B7-2) in EAE and the effect of administration.Methods :Forty-five female C57BL/6 mice were immunized wih 300ug MOG35-55 in compete Freund,s adjuvant (CFA,10mg/ml) to establish EAE model ,then were randomly divided into three groups: the EAE group (n=15),the methylprednisolone (MP)-treated group (n=15) and the interferon (IFN)-.treated group (n=15).Additionally, the other five mice were set as the control group.Saline (0.5ml) was injected intraperitoneally daily at 0-3 days after onset of EAE in EAE group, MP (40mg/kg) was injected intraperitoneally daily at 0-3 days after onset in MP-treated group.IFN-β1а(6.6ug/kg) subcutaneously injected to IFN-treated group which was the same as MP-treated group.Clinical scores were assessed (Benson scores).Infiltration of inflammatory cells and demyelination in white substance of CNS were observed by HE-staining and immunohistochemistry. While the expression of CD80 ,CD86 and TNF-αin brain were detected by Western Blot, respectively.Results: The clinic symptoms of EAE appeared about two weeks post-immunization, including atonic tail, paralysis of limb, staggering gait and stand the difficulties. Pathological study showed there were abundant inflammatory cells infiltrated in the CNS in EAE mice,with typical demyelination in white matter. Compared with the control group, the expression of CD80 ,CD86 and TNF-αin brain were significantly increased in the EAE group (P<0.05).With the treatment of MP ,the expression of CD80 and TNF-αwere significantly decreased (P<0.05),but CD86 increased comparing with the EAE group (P<0.05).With the treatment of IFN, the expression of CD86 significantly increased (P<0.05), but the expression of CD80 and TNF-αdid not experience significant change. Correlation analysis indicated that the expression of TNF-αdisplayed positive correlation with CD80,but not with CD86.Conclusions: The costimulatory molecule CD80 played a leading role in the pathogenesis and progression of EAE,while CD86 could promote the mitigation and recovery of disease. CD80 had a direct or indirect regulation on the expression of TNF-α, and thus caused pathological damages by participating in the inflammatory response of EAE . Thus, CD80 and CD86 could be used as a new target for MS therapy。...