Ablation of “tolerance” and induction of diabetes by virus infection in viral antigen transgenic mice

PS Ohashi, S Oehen, K Buerki, H Pircher, CT Ohashi… - Cell, 1991 - cell.com
PS Ohashi, S Oehen, K Buerki, H Pircher, CT Ohashi, B Odermatt, B Malissen…
Cell, 1991cell.com
To address the mechanisms of tolerance to extrathymic proteins, we have generated
transgenic mice expressing the lymphocytic choriomeningitis viral (LCMV) glycoprotein (GP)
in the β isiet 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-2D b. 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 …
Abstract
To address the mechanisms of tolerance to extrathymic proteins, we have generated transgenic mice expressing the lymphocytic choriomeningitis viral (LCMV) glycoprotein (GP) in the β isiet 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 moiecuies. 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 abollshes peripheral unresponsiveness to the self LCMV GP antigen, resuiting in a CD8+ T cell-mediated diabetes. These data suggest that simllar mechanisms may operate in several so-called "T cell-mediated autoimmune diseases."
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