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Neither B lymphocytes nor antibodies directed against self antigens of the islets of Langerhans are required for development of virus-induced autoimmune diabetes.
Holz, A; Dyrberg, T; Hagopian, W; Homann, D; von Herrath, M; Oldstone, M B.
Afiliação
  • Holz A; Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. aholz@scripps.edu
J Immunol ; 165(10): 5945-53, 2000 Nov 15.
Article em En | MEDLINE | ID: mdl-11067957
We evaluated the role of the humoral arm of the immune response in causing or contributing to virus-induced diabetes. Transgenic mice expressing the nucleoprotein (NP) or glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCMV) under control of the rat insulin promoter (RIP) in pancreatic beta cells (RIP-LCMV) and RIP-LCMV mice with genetic dysfunction of B cells (RIP-LCMV x microMT/microMT) were compared for development of diabetes after challenge with LCMV. After inoculation with LCMV, B and T lymphocytes and macrophages infiltrated into pancreatic islets in RIP-LCMV mice, and over 50% of these mice generated Abs against host insulin or glutamate decarboxylase. However, neither B cells nor the autoantibodies played a direct role in the initiation, kinetics, or severity of the virus-induced diabetes as judged by comparing disease in RIP-LCMV mice to littermates whose functional B cells were genetically eliminated. Furthermore, the quality and quantity of T lymphocyte and macrophage infiltration was similar in the B cell-deficient and non-B cell-deficient RIP-LCMV mice. Although the development of autoantibodies to islet Ags had no direct influence on the pathogenesis of insulin-dependent (type 1) diabetes mellitus, it served as a prediabetes marker, as such autoantibodies were often elevated before the onset of disease. Hence, the RIP-LCMV model is not only useful for understanding the pathogenetic mechanisms of how islets are destroyed and spared but also for evaluating therapeutic strategies before onset of clinical diabetes.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoanticorpos / Autoantígenos / Linfócitos B / Ilhotas Pancreáticas / Diabetes Mellitus Tipo 1 / Vírus da Coriomeningite Linfocítica / Citotoxicidade Celular Dependente de Anticorpos Idioma: En Revista: J Immunol Ano de publicação: 2000 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoanticorpos / Autoantígenos / Linfócitos B / Ilhotas Pancreáticas / Diabetes Mellitus Tipo 1 / Vírus da Coriomeningite Linfocítica / Citotoxicidade Celular Dependente de Anticorpos Idioma: En Revista: J Immunol Ano de publicação: 2000 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos