DIFFERENTIAL RESPONSIVENESS TO INTERFERON-ALPHA IN BETA-CELLS AND NON-BETA-CELLS

Interferon-alpha (IFN-alpha) is important in the innate immune defense , particularly in viral infections, IFN-alpha induces 2',5'A synthetas e, the products of which, 2',5'-oligoadenine nucleotides, activate mRN A degrading enzymes. IFN-alpha is the first detectable cytokine in the insulitis lesion seen in recent-onset IDDM, and insulin promoter dire cted expression of IFN-alpha in transgenic mice leads to development o f IDDM. Here, we demonstrate that IFN-alpha induces 2',5'A synthetase activity only in insulin-producing beta TC3 cells and in isolated sing le rat beta-cells but not in alpha TC3 cells or in isolated rat non-be ta-cells. The increased responsiveness of beta-cells but not non-beta- cells to IFN-alpha with the ensuing activation of the mRNA-degrading 2 ',5'A synthetase system suggests why only the beta-cells are destroyed in the diabetogenic process.