An Ex Vivo Model of Tolerance vs. Rejection: Comparison of Different Signal Transducers and Activators of Transcription, STAT1, STAT4, STAT5 and STAT6
-
Su Metcalfe
and Susan Moffatt-Bruce
Abstract
An ideal for clinical organ transplantation is for the recipient to develop graft-specific immune tolerance. Although tolerance may occur, there is no way of identifying those recipients who are tolerant vs. those still capable of rejecting their graft. Thus immunosuppressive therapy is normally continued throughout life with the attendant risks of infection, neoplasia, and unwanted side effects of the immunosuppressive drugs. A surrogate marker of specific immune non-responsiveness would permit identification of graft-tolerant individuals who may then be weaned off all immunosuppression. Here we present a model which characterises discrete components of a tolerant, vs. aggressive, immune response. In rodents, new populations of tolerant, regulatory cells can be generated for a foreign graft iffirst exposure of the T cell receptor (TCR) to graft antigen coincides with blockade of the CD4 and CD8 co-receptors of the TCR. Once established, this type of peripheral tolerance is very robust. We have exploited an ex vivo model to compare in vivo-derived allo-tolerant lymphocytes with their counterpart which have been primed to reject the same allo-antigen. The model has revealed differential STAT (Signal Transducers and Activators of Transcription) responses associated with tolerance, vs. rejection, which have not been previously described. This approach will identify candidate surrogate markers of immune response status for potential clinical application.
Copyright © 2000 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- European Meeting on Biomarkers of Organ Damage and Dysfunction Selected Papers from the Meeting Held in Cambridge, UK April 3rd-7th, 2000
- Kidney Retrieval Conditions Influence Damage to Renal Medulla: Evaluation by Proton Nuclear Magnetic Resonance (NMR) Spectroscopy
- Citrate, Acetate and Renal Medullary Osmolyte Excretion in Urine as Predictor of Renal Changes after Cold Ischaemia and Transplantation
- Comparison of Proteolytic Enzymes and Glutathione S-Transferase Levels in Non-Heart-Beating Donors' (NHBD) Kidney Perfusates
- Assessment of Non-Heart-Beating Donor (NHBD) Kidneys for Viability on Machine Perfusion
- Low Levels of Urinary Albumin Excretion Are Associated with Cardiovascular Risk Factors in the General Population
- Evaluation of a Fully Automated Assay to Measure C-Telopeptide of Type I Collagen in Serum
- Bone Turnover Markers and Estradiol Level in Postmenopausal Women
- External Quality Assessment of Bone Metabolism Marker Assays. Initial Experiences in a UK NEQAS Programme
- The Monoethylglycinexylidide (MEGX) Test as a Marker of Hepatic Dysfunction in Septic Patients with Pneumonia
- Transforming Growth Factor-β1 as a Surrogate Marker of Hepatic Dysfunction in Chronic Liver Diseases
- A New Approach to the Evaluation of Liver Graft Function by Nuclear Magnetic Resonance Spectroscopy. A Comparative Study between Euro-Collins and University of Wisconsin Solutions
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- Different Time Frames for the Occurrence of Elevated Levels of Cardiac Troponin T and C-Reactive Protein in Patients with Acute Myocardial Infarction
- Determination of Decision Limits for ACS:Systems Cardiac Troponin I
- Stability of Cardiac Troponins and CK-MB Mass Isoenzyme
- Cytokines as Plasma Markers of Abdominal Aortic Aneurysm
- The Early Fall in Levels of S-100 β in Traumatic Brain Injury
- Protein S-100β in Brain and Serum after Deep Hypothermic Circulatory Arrest in Rabbits: Relationship to Perivascular Astrocytic Swelling
- The Effect of Continuous Treatment with Sodium Nitroprusside on the Serum Kinetics of the Brain Marker Protein S-100β in Neonates Undergoing Corrective Cardiac Surgery by Means of Hypothermic Cardiopulmonary Bypass
- Differentiated Therapy with Prostaglandin E1 (Alprostadil) after Orthotopic Liver Transplantation: the Usefulness of Procalcitonin (PCT) and Hepatic Artery Resistive Index (RI) for the Evaluation of Early Graft Function and Clinical Course
- The Postoperative Course of γ-Glutamyl Transpeptidase – a Marker of Cytomegalovirus (CMV) Replication Risk?
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