Fas Is Detectable on {beta} Cells in Accelerated, But Not Spontaneous, Diabetes in Nonobese Diabetic Mice

Fas (CD95) is a potential mechanism of pancreatic [beta] cell death in type 1 diabetes. [beta] cells do not constitutively express Fas but it is induced by cytokines. The hypothesis of this study is that Fas expression should be measurable on [beta] cells for them to be killed by this mechanism. We...

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Published in:The Journal of immunology (1950) 2003-06, Vol.170 (12), p.6292-6297
Main Authors: Darwiche, Rima, Chong, Mark M. W, Santamaria, Pere, Thomas, Helen E, Kay, Thomas W. H
Format: Article
Language:English
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Summary:Fas (CD95) is a potential mechanism of pancreatic [beta] cell death in type 1 diabetes. [beta] cells do not constitutively express Fas but it is induced by cytokines. The hypothesis of this study is that Fas expression should be measurable on [beta] cells for them to be killed by this mechanism. We have previously reported that up to 5% of [beta] cells isolated from nonobese diabetic (NOD) mice are positive for Fas expression by flow cytometry using autofluorescence to identify [beta] cells. We have now found that these are not [beta] cells but contaminating dendritic cells, macrophages, and B lymphocytes. In contrast [beta] cells isolated from NODscid mice that are recipients of T lymphocytes from diabetic NOD mice express Fas 18-25 days after adoptive transfer but before development of diabetes. Fas expression on [beta] cells was also observed in BDC2.5, 8.3, and 4.1 TCR-transgenic models of diabetes in which diabetes occurs more rapidly than in unmodified NOD mice. In conclusion, Fas is observed on [beta] cells in models of diabetes in which rapid [beta] cell destruction occurs. Its expression is likely to reflect differences in the intraislet cytokine environment compared with the spontaneous model and may indicate a role for this pathway in [beta] cell destruction in rapidly progressive models.
ISSN:0022-1767
1550-6606