title: Comparison of tolerated and rejected islet grafts: a gene expression study.
abstract: Recently we showed that donor-specific tolerance to MHC-matched islet allografts in diabetic NOD mice could be induced by simultaneous islet and bone marrow transplantation. Mononuclear cell infiltration surrounding the islets was also found in tolerated grafts. In this study, we compared gene expression in the tolerated and rejected islet grafts by using Affymetrix Murine U74A oligonucleotide arrays. To confirm the results of microarray analysis, we performed real-time PCR and RNase protection assay on selected genes. Of over 12,000 genes studied, 57 genes were expressed at consistently higher levels in tolerated islet grafts, and 524 genes in rejected islet grafts. Genes from a variety of functional clusters were found to be different between rejected and tolerated grafts. In the rejected islet grafts, a number of T-cell surface markers and of cytotoxicity-related genes were highly expressed. Also in the rejected grafts, a number of cytokines and chemokines and their receptors were highly expressed. The differential expression of selected genes found by microarray analysis was also confirmed by real-time PCR and RNase protection assay. Our results indicated that gene microarray analysis can help us to detect gene expression differences representative of the biologic mechanisms of tolerance and rejection.
authors.affiliation: Diabetes Institute for Immunology and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Berg
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Brett
authors.initials: B
authors.lastname: Levay-Young
authors.forename: Neal
authors.initials: N
authors.lastname: Heuss
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Pan
authors.forename: Nicole
authors.initials: N
authors.lastname: Kirchhof
authors.forename: David E R
authors.initials: DE
authors.lastname: Sutherland
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Hering
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics*; D007113:Immunity, Innate / Q000235:genetics; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D020411:Oligonucleotide Array Sequence Analysis; D019707:Receptors, Chemokine / Q000235:genetics; D018121:Receptors, Cytokine / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine