Analysis of the Innate and Adaptive Phases of Allograft Rejection by Cluster Analysis of Transcriptional Profiles

Christopher, Kenneth B.; Mueller, Thomas; Ma, Chunyan; Liang, Yurong; Perkins, David L.

doi:10.4049/jimmunol.169.1.522

Cited by 52 publications

(28 citation statements)

References 57 publications

(39 reference statements)

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“…Tissue injury up-regulates proinflammatory mediators, inducing a robust innate immune response that in turn further promotes inflammation (LaRosa et al, 2007). The innate immune response occurs prior to and independently of the adaptive immune response (Christopher et al, 2002;He et al, 2002;2003), as RAG-deficient cardiac transplant recipients experience comparable cellular infiltration, chemokine receptor expression and pro-inflammatory cytokine expression with wild-type recipients 1 day posttransplantation (He et al, 2002).…”

Section: Ischemia-reperfusion Injurymentioning

confidence: 99%

Cell-Based Therapies in the Prevention of Solid Organ Transplant Rejection

Morelli¹,

Divito²

2012

American Journal of Immunology

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Problem statement:Organ transplantation is a life-saving and increasingly common procedure, as it often serves as the only treatment available for end-stage organ disease. Although the constant development of new and more effective immunosuppressive drugs has revolutionized the prevention and treatment of acute graft rejection, these drugs have significant toxicity, greatly increase patient susceptibility to neoplasms and infection and exert little impact on chronic rejection. Approach: The literature was reviewed to illuminate the mechanisms by which the anti-donor immune response is initiated and how cellular therapies impact this response. Results: Data show that Donor Specific Transfusion, Apoptotic Cell therapies and Dendritic Cell therapies all function as a source of alloantigen to suppress the anti-donor T cell response. Conclusion: Cellular therapies hold promise in the prevention of solid organ allograft rejection, but require optimization and study in large animal models before clinical implementation.

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Section: Ischemia-reperfusion Injurymentioning

confidence: 99%

Cell-Based Therapies in the Prevention of Solid Organ Transplant Rejection

Morelli¹,

Divito²

2012

American Journal of Immunology

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“…To address these limitations, the effects of various interventions on grafted organs in mouse and rat models have been assessed using expression microarrays. The overall dynamics of gene expression after cardiac transplant in mice (48)(49)(50)(51) and rats (52, 53) have been assessed. A collection of cytotoxic T-lymphocyte-associated transcripts leading to the development of tubulitis was found in mouse kidney allografts (54).…”

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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“…Total RNA was isolated and reverse transcribed, according to standard techniques (21). Direct detection of the PCR product was monitored by measuring an increase in fluorescence due to the binding of SYBR Green to dsDNA.…”

Section: Gene Expression Analysis By Real-time Pcrmentioning

confidence: 99%

The Allograft Defines the Type of Rejection (Acute versus Chronic) in the Face of an Established Effector Immune Response

Chalasani

Konieczny

et al. 2004

The Journal of Immunology

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Transplanted organs fail due to either acute or chronic rejection. The prevailing view is that the nature or magnitude of the recipient’s immune response to donor Ags determines the type of rejection. In variance with this view, we show in this study that the status of the graft itself plays a dominant role in defining the type of rejection even in the face of an established alloimmune response. Using adoptive transfer mouse models in which the graft is exposed to a constant number of effector lymphocytes, we found that newly transplanted heart allografts are rejected acutely, while healed-in allografts undergo chronic rejection. Acute rejection of healed-in allografts was largely recapitulated by subjecting the grafts to ischemia-reperfusion injury similar to that present in newly transplanted organs. Ischemia-Reperfusion injury altered the outcome of rejection by enhancing the accumulation of effector T cells within the graft. The accumulation of effector T cells in the graft was dependent on the presence of both ischemia-reperfusion injury (inflammation) and alloantigens. These findings demonstrate that the graft plays a dominant role in shaping the outcome of rejection by controlling the trafficking of effector T cells.

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Analysis of the Innate and Adaptive Phases of Allograft Rejection by Cluster Analysis of Transcriptional Profiles

Cited by 52 publications

References 57 publications

Cell-Based Therapies in the Prevention of Solid Organ Transplant Rejection

Cell-Based Therapies in the Prevention of Solid Organ Transplant Rejection

Novel Insights into Lung Transplant Rejection by Microarray Analysis

The Allograft Defines the Type of Rejection (Acute versus Chronic) in the Face of an Established Effector Immune Response

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