Identification of gene expression profile in tolerizing murine cardiac allograft by costimulatory blockade

Yuichi Matsui, Akio Saiura, Yasuhiko Sugawara, Masataka Sata, Katsutoshi Naruse, Hideo Yagita, Takahide Kohro, Chikage Mataki, Akashi Izumi, Takuhiro Yamaguchi, Takashi Minami, Toshiko Sakihama, Sigeo Ihara, Hiroyuki Aburatani, Takao Hamakubo, Tatsuhiko Kodama, Masatoshi Makuuchi

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


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-γ-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.

Original languageEnglish
Pages (from-to)199-208
Number of pages10
JournalPhysiological Genomics
Publication statusPublished - 2004 Jan


  • Chemokine
  • DNA microarray
  • Immunologic tolerance
  • Interferon-γ
  • Transplantation


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