A CD8+ T-lymphocyte-mediated and CD4+ T-lymphocyte-independent autoimmune diabetes of early onset in transgenic mice.

While transgenic mice expressing tumour necrosis factor-alpha under the control of the beta-cell-specific insulin promoter display a marked lymphocytic infiltration of the islets, they never develop insulin-dependent diabetes mellitus (IDDM). In striking contrast, "double" transgenic mice whose beta cells express both tumour necrosis factor-alpha as well as the co-stimulatory B7-1 molecule all develop IDDM at an early age. Furthermore, administration of anti-CD8 but not anti-CD4 immunoglobulins prevents diabetes onset. These results indicate that while tumour necrosis factor-alpha induced lymphocytic infiltration is not sufficient to effect beta-cell destruction, locally co-stimulated islet-infiltrating CD8+ T lymphocytes could play a critical role in the development of IDDM.