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