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 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.
Darwiche
Rima
R
St. Vincent's Institute of Medical Research, Fitzroy, Australia, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Chong
Mark M W
MM
Santamaria
Pere
P
Thomas
Helen E
HE
Kay
Thomas W H
TW
D000818:Animals; D001324:Autoantigens / Q000032:analysis; D002352:Carrier Proteins / Q000096:biosynthesis / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D053590:Interleukin 1 Receptor Antagonist Protein; D007515:Islets of Langerhans / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012097:Repressor Proteins / Q000096:biosynthesis / Q000502:physiology; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000502:physiology; D013194:Staining and Labeling; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D019014:fas Receptor / Q000032:analysis* / Q000096:biosynthesis
D001324:Autoantigens; D002352:Carrier Proteins; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012097:Repressor Proteins; D012795:Sialoglycoproteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D019014:fas Receptor; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1