Expression of pancreatic islet MHC class I, insulin, and ICA 512 tyrosine phosphatase in low-dose streptozotocin-induced diabetes in mice.
Activated immune cells contribute to the development of diabetes mellitus in multiple low-dose streptozotocin-treated mice. However, a role in the process for MHC Class I restricted T-cells remains a matter of debate. In this study, we examined by confocal microscopy the pancreatic expression of MHC Class I protein, insulin, and ICA 512 protein tyrosine phosphatase in C57BL/Ks mice given 40 mg/kg bw streptozotocin IP on 5 consecutive days. All animals were hyperglycemic from Day 7 and onwards. A loss of ICA 512 from the central portions of the islets was noted on Day 3. On Day 7, an increase in MHC Class I expression, confined primarily to immune cells in the exocrine pancreas and the periinsular areas, was detected. Later, several MHC class I/glucagon and some MHC class I/insulin double-positive cells were found. The insulitis was maximal on Day 14 and declined thereafter. The induction of MHC Class I expression in endocrine cells, occuring only after the cellular infiltration and when the animals were diabetic, indicates that the immune component of the disease does not depend on MHC Class I-restricted cytotoxic T-cells but rather comprises a non-antigen-specific process. (J Histochem Cytochem 48:761-767, 2000)
Li
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Z
Departments of Medical Sciences, Uppsala University, Uppsala, Sweden.
Zhao
L
L
Sandler
S
S
Karlsson
F A
FA
D000818:Animals; D001324:Autoantigens / Q000096:biosynthesis*; D001786:Blood Glucose / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000096:biosynthesis; D006183:H-2 Antigens / Q000096:biosynthesis*; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis*; D011817:Rabbits; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D013311:Streptozocin
D001324:Autoantigens; D001786:Blood Glucose; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D007328:Insulin; D008565:Membrane Proteins; D013311:Streptozocin; D005934:Glucagon; C516862:PTPRN protein, human; D017027:Protein Tyrosine Phosphatases; C516863:Ptprn protein, mouse; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8