On the role of peripheral macrophages during active experimental allergic encephalomyelitis (EAE)

Experimental allergic encephalitis (EAE) is an experimental autoimmune infl ammatory condition of the central nervous system (CNS) that serves as a dis ease model for multiple sclerosis (MS). The primary effector mechanisms of the immune system leading to tissue destruction during EAE remain still con troversial. T-cells, microglia, and macrophages infiltrating the brain pare nchyma are suggested to be involved. To clarify the role of these cells dur ing disease Lewis rats were immunised with different immunisation protocols : Immunisation with myelin basic protein (MBP) in complete Freunds adjuvant (CFA) containing high dose of mycobacterial components induced severe dise ase, whereas immunisation with low dose of mycobacterial components;induced only mild disease. Severely and mildly diseased animals were analysed with respect to infiltration of T-cells, macrophages and upregulation of MHC cl ass II molecules on microglia in the brain. All immunised rats showed high T-cell infiltration accompanied by microglia activation. The degree of disease and the infiltration of macrophages vari ed with dose of adjuvant. Lowering the dose of adjuvant prevented the devel opment of disease but also the influx of peripheral macrophages into the br ain without affecting the peripheral T-cell response to the autoantigen. Th us, appearance of (autoreactive) T-cells in the brain and microglia activat ion were probably not sufficient for development of disease. It can be concluded that peripheral macrophages play an essential or even k ey role in the pathogenesis of active EAE.