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

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

doi:10.1152/physiolgenomics.00086.2003

Cited by 25 publications

(16 citation statements)

References 22 publications

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“…We showed that tolerated allografts exhibit strong infiltration and a marked expression of a number of genes for molecules usually considered as pro-inflammatory factors (including chemokines, cytokines, and cytotoxicity-or activation-related genes). High expres- sion of these "proinflammatory" genes may therefore not be necessarily considered as predictive or as diagnosis of graft failure (28). Expression of these genes in tolerated allografts could reflect the presence of both effector cells and regulatory T cells.…”

Section: Discussionmentioning

confidence: 99%

New Evidence for a Role of Allograft Accommodation in Long-Term Tolerance

Heslan

Renaudin²,

Thébault³

et al. 2006

Transplantation

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Section: Discussionmentioning

confidence: 99%

New Evidence for a Role of Allograft Accommodation in Long-Term Tolerance

Heslan

Renaudin²,

Thébault³

et al. 2006

Transplantation

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“…A set of genes (TGF-ß2, ppENK, GM2a, GITR, IL-1R2) were identified by SAGE screening that are specifically upregulated in regulatory T cells associated with tolerance of skin allografts (41,42). Matsui et al identified two genes (H2-Ea, Frzb), which are highly expressed in long-term surviving heart allografts (43). In this model long-term survival was induced by costimulatory blockade.…”

Section: Marker For Monitoring Of T-cell Modulating Therapiesmentioning

confidence: 99%

Identification of Gene Markers for the Prediction of Allograft Rejection or Permanent Acceptance

Sawitzki

Bushell

Steger

et al. 2007

American Journal of Transplantation

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The clinical success of new treatment strategies aiming on inducing permanent graft acceptance will rely on the ability to determine whether specific unresponsiveness to donor alloantigens has developed and for how long it is maintained. To identify markers for such posttransplant monitoring, genes differentially expressed by graft infiltrating leukocytes during tolerance induction or rejection after kidney transplantation in rats were compared. A subsequently performed full kinetic analysis in two different transplant models, kidney and heart, in two species, rat and mouse identified two markers (TOAG-1, a -1,2-mannosidase) with high specificity and reproducibility, which are highly expressed during induction and maintenance of acceptance, and downregulated during rejection. Expression level of these markers showed a strong positive correlation with graft function. In addition, expression of both genes was downregulated in the peripheral blood and the graft prior to rejection, suggesting that these markers may be useful for monitoring in clinical transplantation where peripheral blood is the most easily accessible patient sample. Interestingly, downregulation of TOAG-1 and a -1,2-mannosidase expression occurred in graft infiltrating cells and expression of both genes was also downregulated after T-cell activation in vitro.

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“…Analyses of the gene expression profile changes of an experimental immunosuppressant on rat kidney allografts (63), anti-CD80 and anti-CD86 antibodies on mouse cardiac allografts (64), and anti-CD40 and anti-LFA antibodies (65) on mouse tracheal allografts have been tested to explore gene expression changes associated with attenuation of rejection in these models. A group of chemokine genes was found to be up-regulated in IFN-␥-knockout cardiac recipient mice compared with wild-type mice (66), and a set of genes was associated with IFN regulatory factor-1-deficient mouse cardiac recipients (67).…”

Section: Microarray Gene Expression Analysis Of Nonhuman Transplant Mmentioning

confidence: 99%

Novel Insights into Lung Transplant Rejection by Microarray Analysis

Lande

Patil

Li³

et al. 2007

Proceedings of the American Thoracic Society

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Gene expression microarrays can estimate the prevalence of mRNA for thousands of genes in a small sample of cells or tissue. Organ transplant researchers are increasingly using microarrays to identify specific patterns of gene expression that predict and characterize acute and chronic rejection, and to improve our understanding of the mechanisms underlying organ allograft dysfunction. We used microarrays to assess gene expression in bronchoalveolar lavage cell samples from lung transplant recipients with and without acute rejection on simultaneous lung biopsies. These studies showed increased expression during acute rejection of genes involved in inflammation, apoptosis, and T-cell activation and proliferation. We also studied gene expression during the evolution of airway obliteration in a murine heterotopic tracheal transplant model of chronic rejection. These studies demonstrated specific patterns of gene expression at defined time points after transplantation in allografts, whereas gene expression in isografts reverted back to that of native tracheas within 2 wk after transplantation. These studies demonstrate the potential power of microarrays to identify biomarkers of acute and chronic lung rejection. The application of new genetic, genomic, and proteomic technologies is in its infancy, and the microarray-based studies described here are clearly only the beginning of their application to lung transplantation. The massive amount of data generated per tissue or cell sample has spawned an outpouring of invention in the bioinformatics field, which is developing methodologies to turn data into meaningful and reproducible clinical and mechanistic inferences. Keywords: allograft rejection; lung transplantation; microarrayLung and heart-lung transplants, introduced into clinical practice in 1981, have now been performed in over 20,000 individuals worldwide for whom effective medical therapy was not available (1). These procedures have been highly beneficial for many recipients, with 2-yr survival rates of approximately 70% and dramatic improvements in quality of life. Despite these remarkable successes, problems remain, and long-term survival rates for lung transplant recipients are considerably lower than those observed in kidney, heart, and liver recipients. This is due, in large part, to the development of chronic allograft rejection despite administration of immunosuppressive medications.

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

Cited by 25 publications

References 22 publications

New Evidence for a Role of Allograft Accommodation in Long-Term Tolerance

New Evidence for a Role of Allograft Accommodation in Long-Term Tolerance

Identification of Gene Markers for the Prediction of Allograft Rejection or Permanent Acceptance

Novel Insights into Lung Transplant Rejection by Microarray Analysis

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