Summary
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.
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Abbreviations
- FACS:
-
Fluorescence-activated cell sorter
- IDDM:
-
insulin-dependent diabetes mellitus
- i.p.:
-
intraperitoneal injection
- mAb:
-
monoclonal antibody
- NOD:
-
non obese diabetic
- TNFα:
-
tumour necrosis factor alpha
References
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Herrera, P.L., Harlan, D.M., Fossati, L. et al. A CD8+ T-lymphocyte-mediated and CD4+ T-lymphocyte-independent autoimmune diabetes of early onset in transgenic mice. Diabetologia 37, 1277–1279 (1994). https://doi.org/10.1007/BF00399802
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DOI: https://doi.org/10.1007/BF00399802