Differential Responsiveness to Interferon-α in β-Cells and Non-β-Cells

Interferon-α (IFN-α) is important in the innate immune defense, particularly in viral infections. IFN-α induces 2ʹ,5ʹA synthetase, the products of which, 2ʹ,5ʹ-oligoadenine nucleotides, activate mRNA degrading enzymes. IFN-α is the first detectable cytokine in the insulitis lesion seen in recent-onset IDDM, and insulin promoter directed expression of IFN-α in transgenic mice leads to development of IDDM. Here, we demonstrate that IFN-α induces 2ʹ,5ʹA synthetase activity only in insulin-producing βTC3 cells and in isolated single rat β-cells but not in αTC3 cells or in isolated rat non-β-cells. The increased responsiveness of β-cells but not non-β-cells to IFN-α with the ensuing activation of the mRNA-degrading 2ʹ,5ʹA synthetase system suggests why only the β-cells are destroyed in the diabetogenic process.