Identification of early tolerance regulator genes induced by allochimeric therapy using microarray-based genomewide scan.
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.
Liu
D
D
Dumont-UCLA Transplant Center, Department of Surgery, David Geffen School of Medicine, Los Angeles, California, USA.
Shen
X-D
XD
Fang
Z
Z
Gao
F
F
Semiletova
N
N
Cao
M-J
MJ
Busuttil
R W
RW
Kupiec-Weglinski
J W
JW
Ghobrial
R M
RM
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