Chronic experimental autoimmune encephalomyelitis induced by the 89-101 myelin basic protein peptide in B10RIII (H-2r) mice.
Development of experimental allergic encephalomyelitis (EAE) in the SJL (H-2s) mice is associated with a T cell-dependent autoimmune response to the C-terminal part of the myelin basic protein (MBP). In this study the influence of both H-2 and non-H-2 genetic background on EAE induced with the MBP89-101 peptide is described. Analysis of different H-2q haplotype strains, B10G, B10Q, SWR and NFR/N, showed that the B10 background is relatively resistant to disease induction. Both SWR and NFR/N were susceptible to EAE showing that the H-2q haplotype is permissive for EAE development induced with MBP89-101 and that the T cell receptor (TcR) haplotype or complement C5 deficiency exert no significant influence on disease susceptibility. In a series of H-2-congenic strains on the B10 background only B10RIII (H-2r) mice were susceptible to EAE. The B10RIII mice developed a severe EAE with early onset and chronic progressive or relapsing course of disease. In addition, B10RIII mice treated with Freund's complete adjuvant and pertussis toxin alone showed an early monophasic disease. The clinical observations were confirmed by immunohistopathologic analysis of the central nervous system. In these studies, we also applied antibodies to different TcR V beta elements which showed no specific limitation of the used TcR among infiltrating T cells in the target tissue in any of the strains. It is concluded that an MBP peptide-specific disease can be induced in three different haplotypes and it is possible that shared structures between the As, Aq and Ar molecules are of importance for the trigger of encephalitogenic T cells with different TcR V elements. The presently described chronic EAE model induced in the B10RIII mice will be of value as a model for multiple sclerosis.
Jansson
L
L
Department of Medical and Physiological Chemistry, Uppsala University, Sweden.
Olsson
T
T
Höjeberg
B
B
Holmdahl
R
R
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D002531:Cerebellum / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006239:Haplotypes; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D037342:Pertussis Toxin; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000276:immunology
D000276:Adjuvants, Immunologic; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin