title: Identification of early tolerance regulator genes induced by allochimeric therapy using microarray-based genomewide scan.
abstract: We have demonstrated that peri- or postoperative delivery of allochimeric [a1h(u)]-RT1.A(a) class I major histocompatibility complex molecules with donor-type (RT1A(u)) immunogenic epitopes presented in recipient-type (RT1A(a)) sequences induced donor-specific tolerance in ACI (RT1a) recipients of WF (RT1u) heart allografts. A genomic scan during the early posttransplant period was performed to elucidate the underlying operative mechanisms. A rat genome study after transplantation was carefully designed using Affymetrix Rat Genome 230 2.0 Array. The allochimeric treatment group is 3-day cyclosporine (CsA)-treated ACI recipients that accepted Wistar Furth RT1u cardiac allografts with postoperative dosage of allochimeric molecules, while the control is 3-day CsA-treated ACI recipients of WF cardiac allografts. All the samples were harvested 5 days after heart transplant as the early stage of tolerance detection. Following array data normalization and modeling, we compared the above two treatment groups and identified a total of 250 tolerance regulator genes induced by allochimeric molecules only.
authors.affiliation: Dumont-UCLA Transplant Center, Department of Surgery, David Geffen School of Medicine, Los Angeles, California, USA.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: X-D
authors.initials: XD
authors.lastname: Shen
authors.forename: Z
authors.initials: Z
authors.lastname: Fang
authors.forename: F
authors.initials: F
authors.lastname: Gao
authors.forename: N
authors.initials: N
authors.lastname: Semiletova
authors.forename: M-J
authors.initials: MJ
authors.lastname: Cao
authors.forename: R W
authors.initials: RW
authors.lastname: Busuttil
authors.forename: J W
authors.initials: JW
authors.lastname: Kupiec-Weglinski
authors.forename: R M
authors.initials: RM
authors.lastname: Ghobrial
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology*; D016678:Genome; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance / Q000235:genetics*; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011912:Rats, Inbred ACI; D011920:Rats, Inbred WF; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology