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. Further, 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.