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Publication : Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice.

First Author  Ohashi PS Year  1991
Journal  Cell Volume  65
Issue  2 Pages  305-17
PubMed ID  1901764 Mgi Jnum  J:81285
Mgi Id  MGI:2448775 Doi  10.1016/0092-8674(91)90164-t
Citation  Ohashi PS, et al. (1991) Ablation of 'tolerance' and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65(2):305-17
abstractText  To address the mechanisms of tolerance to extrathymic proteins, we have generated transgenic mice expressing the lymphocytic choriomeningitis viral (LCMV) glycoprotein (GP) in the beta islet cells of the pancreas. The fate of LCMV GP-specific T cells was followed by breeding the GP transgenic mice with T cell receptor transgenic mice, specific for LCMV and H-2Db. These studies suggest that 'peripheral tolerance' of self-reactive T cells does not involve clonal deletion, clonal anergy, or a decrease in the density of T cell receptors or accessory molecules. Instead, this model indicates that self-reactive cytotoxic T cells may remain functionally unresponsive, owing to a lack of appropriate T cell activation. Infection of transgenic mice with LCMV readily abolishes peripheral unresponsiveness to the self LCMV GP antigen, resulting in a CD8+ T cell-mediated diabetes. These data suggest that similar mechanisms may operate in several so-called 'T cell-mediated autoimmune diseases.'
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