Identification of gene expression profile in tolerizing murine cardiac allograft by costimulatory blockade.
The induction of specific tolerance would be the ultimate achievement in transplant immunology, but the precise mechanisms of immunologic tolerance remain largely unknown. Here, we investigated global gene expression analysis in tolerizing murine cardiac allografts by means of oligonucleotide microarrays. Tolerance induction was achieved in cardiac allografts from BALB/c to C57BL/6 mice by daily intraperitoneal injection of anti-CD80 and anti-CD86 monoclonal antibodies (mAbs). Comparative analysis revealed 64 genes to be induced more extensively in the tolerizing than in the syngeneic isografts, and 16 genes than in the rejecting allografts. Two genes were specifically upregulated in the tolerizing allografts. In the tolerizing allografts there were induced marked expressions of a number of genes for pro-inflammatory factors, including interferon-gamma-inducible cytokines and chemokines, as well as apoptosis-related genes, which were also upregulated in the rejecting allografts. Moreover, these gene expression patterns continued to be upregulated more than 70 days posttransplant. These results provide evidence that immunologic tolerance can be induced and maintained in the presence of prominent pro-inflammatory gene expression in vivo.
Matsui
Yuichi
Y
Department of Hepato-Biliary-Pancreatic and Transplantation Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Saiura
Akio
A
Sugawara
Yasuhiko
Y
Sata
Masataka
M
Naruse
Katsutoshi
K
Yagita
Hideo
H
Kohro
Takahide
T
Mataki
Chikage
C
Izumi
Akashi
A
Yamaguchi
Takuhiro
T
Minami
Takashi
T
Sakihama
Toshiko
T
Ihara
Sigeo
S
Aburatani
Hiroyuki
H
Hamakubo
Takao
T
Kodama
Tatsuhiko
T
Makuuchi
Masatoshi
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology* / Q000502:physiology; D018122:B7-1 Antigen / Q000276:immunology* / Q000502:physiology; D051940:B7-2 Antigen; D016000:Cluster Analysis; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D005786:Gene Expression Regulation / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006084:Graft Rejection / Q000235:genetics; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D016027:Heart Transplantation / Q000379:methods*; D007108:Immune Tolerance / Q000235:genetics* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins