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. 1998 Oct 1;12(13):1255–1265. doi: 10.1096/fasebj.12.13.1255

Table 3.

Lessons for virus‐induced IDDM learned from the molecular mimicry transgenic model

  1. Lymphocytes in periphery are ignorant (tolerant) to the transgene (viral protein)

    1. Activated by cytokines or activation molecules

      • IFN‐γ

      • B7.1

    2. Activated by virus (specific or cross‐reactive to the transgene) infection

  2. IDDM can be rapid (<21 days) or slow (30 to 120 days) in onset

    1. Rapid onset

      • transgene in target cell (tissue) only

      • CD8+ T cell dependent

      • high affinity CTL

    2. Slow onset

      • transgene in target cell and thymus

      • CD8+ T and CD4+ T cell dependent

      • low affinity CTL

      • association of thymic expression and MHC haplotype for time to develop IDDM

        • 4 to 5 log difference in affinity H‐2d vs. H‐2b

  3. IDDM caused by CD8+ antiviral (self) CTL

    • dependent on perforin

  4. IDDM dependent on specific cytokine profile in the islets

    • dependent on interferon‐γ

    • associated with Th1 helper cytokine profile

    • prevented by IL‐4

  5. IDDM requires at least one virus (antiself) CD8+ specific T cell per 1500 total CD8+ T cells; 1/6000 or less does not cause diabetes