title: Monitoring gene expression of TNFR family members by beta-cells during development of autoimmune diabetes.
abstract: Autoimmune diabetes results from destruction of pancreatic beta-cells by islet-infiltrating leukocytes. Different molecular mechanisms seem to be involved in this destruction but the results from many studies have not provided a clear picture so far. Therefore, we have developed a multiplex single-cell reverse transcription polymerase chain reaction to analyze the expression of genes of the tumor necrosis factor receptor (TNFR) family in pancreatic beta-cells during the development of autoimmune diabetes in a TCR-HA x INS-HA double transgenic as well as a non-obese diabetic (NOD) animal model. To this end we have followed the expression of cell surface receptors of the TNFR family in NOD mice as well as in double transgenic mice that express in their T cells class II MHC-restricted TCR specific for peptide 111 - 119 from influenza hemagglutinin (TCR-HA) as well as hemagglutinin under the control of the rat insulin promoter (INS-HA). Both types of mice develop insulitis and diabetes spontaneously. The data show a significant increase in the expression of Fas and TNFR2 (p75) during the development of insulitis, whereas TNFR1 (p55) is already expressed in beta-cells before the onset of insulitis. As ligands for these receptors are already expressed at high levels during the phase of insulitis, it is possible that beta-cell death is regulated by intracellular inhibitors of apoptosis pathways.
authors.affiliation: Institut Necker, INSERM U373, Paris, France.
authors.forename: U
authors.initials: U
authors.lastname: Walter
authors.forename: A
authors.initials: A
authors.lastname: Franzke
authors.forename: A
authors.initials: A
authors.lastname: Sarukhan
authors.forename: C
authors.initials: C
authors.lastname: Zober
authors.forename: H
authors.initials: H
authors.lastname: von Boehmer
authors.forename: J
authors.initials: J
authors.lastname: Buer
authors.forename: O
authors.initials: O
authors.lastname: Lechner
authors.forename: A
authors.initials: A
authors.lastname: Frantzke
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D017209:Apoptosis; D002460:Cell Line; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D005810:Multigene Family / Q000235:genetics*; D010446:Peptide Fragments / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019014:fas Receptor / Q000235:genetics
chemical_list: D015703:Antigens, CD; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007328:Insulin; D010446:Peptide Fragments; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D019014:fas Receptor