Autoimmune demyelination in transgenic E alpha d-positive A.CA mice. Comparison with E-negative A.CA mice.
A body of literature exists implicating the major histocompatibility complex class II E molecule in development of immune tolerance and/or immunosuppression. To define better the regulatory mechanisms underlying susceptibility to experimental autoimmune encephalomyelitis, an autoimmune condition displaying major histocompatibility complex-II dependence, disease was induced in transgenic mice expressing a major histocompatibility complex-II E alpha d-transgene. This was compared with experimental autoimmune encephalomyelitis induced in age-matched E-negative, non-transgenic mice of the same strain. The results showed that experimental autoimmune encephalomyelitis could be induced by adoptive transfer methodology in both transgenic and non-transgenic mice of the A.CA (H-2f) strain. Virtually no differences were observed between the two mouse types with regard to disease onset, course, and neuropathology. The main difference noted was within nonirradiated recipient subgroups where the nonirradiated transgenic A.CA mice demonstrated greater inflammation and demyelination than the nonirradiated, non-transgenic mice throughout the disease course. Thus, the results did not support the idea that the E molecule, per se, is involved in the induction of tolerance or immunosuppressive mechanisms protecting against autoimmunity. In addition, histologic changes in the central nervous system of the A.CA strain, both transgenic and non-transgenic, differed in several respects from the changes observed in other more commonly studied susceptible strains. In A.CA mice, polymorphonuclear cells were a more prominent component of the acute inflammatory infiltrate and in chronic disease, large aggregates of lipid-laden macrophages and cholesterol clefts were present within white matter lesions. The present approach, using genetic manipulation of the immune system, may have relevance to the study of disease mechanisms in other putative autoimmune demyelinating disorders such as multiple sclerosis.
Cross
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AH
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York.
Ishikawa
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Raine
C S
CS
Diamond
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B
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic
D000949:Histocompatibility Antigens Class II