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

✍ Scribed by P. L. Herrera; D. M. Harlan; L. Fossati; S. Izui; J. Huarte; L. Orci; J. D. Vassalli; P. Vassalli

Publisher
Springer
Year
1994
Tongue
English
Weight
593 KB
Volume
37
Category
Article
ISSN
0012-186X

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✦ Synopsis

While transgenic mice expressing tumour necrosis factor-alpha under the control of the betacell-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 pre-vents 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.

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