On the role of peripheral macrophages during active experimental allergic encephalomyelitis (EAE).
Experimental allergic encephalitis (EAE) is an experimental autoimmune inflammatory condition of the central nervous system (CNS) that serves as a disease model for multiple sclerosis (MS). The primary effector mechanisms of the immune system leading to tissue destruction during EAE remain still controversial. T-cells, microglia, and macrophages infiltrating the brain parenchyma are suggested to be involved. To clarify the role of these cells during 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 disease, 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 class 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 varied with dose of adjuvant. Lowering the dose of adjuvant prevented the development of disease but also the influx of peripheral macrophages into the brain without affecting the peripheral T-cell response to the autoantigen. Thus, appearance of (autoreactive) T-cells in the brain and microglia activation were probably not sufficient for development of disease. It can be concluded that peripheral macrophages play an essential or even key role in the pathogenesis of active EAE.
Imrich
H
H
Institut für Hirnforschung, Universität Tübingen, Federal Republic of Germany.
Harzer
K
K
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001921:Brain / Q000166:cytology / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005434:Flow Cytometry; D005620:Freund's Adjuvant; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D017628:Microglia / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000942:Antigens, Bacterial; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D005620:Freund's Adjuvant