E-GEOD-582 - Transcription profiling of tolerizing murine cardiac allograft to understand the precise mechanisms of immunological tolerance
Submitted on 8 August 2003, released on 15 December 2007, last updated on 27 March 2012
C57/BL6 to C57/BL6; Balb/c to C57/BL6; Balb/c to C57/BL6 with anti CD80/86 mAb; Identificaton of gene expression profile in tolerizing murine cardiac allograft by co-stimulatory blockade. The induction of specific tolerance would be the ultimate achievement in transplant immunology, but the precise mechanisms of immunological 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 CD86 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 proinflammatory 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 post transplant. These results provide evidence that immunological tolerance can be induced and maintained in the presence of prominent proinflammatory gene expression in vivo.
transcription profiling by array, co-expression, compound treatment, time series
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. Physiol Genomics 15(3):199-208 (2003)