[Immunological analysis of HTLV-I env-pX transgenic rat with various collagen vascular diseases].
Human T lymphocyte virus type-I (HTLV-I) is an etiologic agent of not only adult T cell leukemia but also HTLV-I associated myelopathy/tropical spastic paraparesis, HTLV-I associated arthropathy and other immunological disorders, such as Sjögren syndrome, dermatitis, polymyositis, and uveitis. We recently reported that a wide spectrum of collagen vascular diseases, including inflammatory arthropathy resembling rheumatoid arthritis, myocarditis, dermatitis, necrotizing arteritis, myositis and sialoadenitis similar to Sjögren's syndrome, developed in the transgenic rat carrying HTLV-I env-pX region under the control of its own long terminal repeat (env-pX rat). To investigate the pathogenetic role of these diseases, cell surface molecules and functions of lymphocytes from env-pX rats were examined in this study. In env-pX rats with diseases, not only infiltrating lymphocytes in the inflammatory sites but also peripheral lymphocytes expressed a large number of co-stimulating molecules such as CD80/86 and ICAM-1, compared with those of normal rats or rats with adjuvant-induced arthritis or myosin-induced myocarditis. Moreover, the expression of CD80/86 and ICAM-1 was already up-regulated on the surface of peripheral lymphocytes in env-pX rat before developing any diseases. Lymphocytes, taken from env-pX rats immunized with myosin in vivo, showed significantly higher cellular response against myosin in vitro than those of normal rats. Lymphocytes from env-pX rats also showed the hyper-reactivity to the stimulation by super-antigens, but no significant difference of the usage of T cell receptor V beta was found compared with those of normal rats. These results suggest that the env-pX transgene may induce the high expression of CD80/86 and ICAM-1 on the lymphocytes and the resulting hyper-immune responsiveness in env-pX rats.
Nakamaru
Y
Y
Department of Otorhinolaryngology, Hokkaido University School of Medicine, Sapporo, Japan.
D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D003095:Collagen Diseases / Q000209:etiology*; D005814:Genes, Viral; D015752:Genes, env; D016355:Genes, pX; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009218:Myosins / Q000276:immunology; D011401:Promoter Regions, Genetic; D051381:Rats; D011917:Rats, Inbred Lew; D012091:Repetitive Sequences, Nucleic Acid; D015854:Up-Regulation
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1; D009218:Myosins