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      Patients on Chronic Hemodialysis Have No Intrinsic Lymphocyte Defect upon Stimulation with Interleukin-2, Interleukin-15 or Tumor Necrosis Factor-Alpha

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          Abstract

          Background: Patients on chronic hemodialysis (HD) suffer from general immune incompetence, resulting in a high incidence of infectious complications, impaired response to vaccinations and a high incidence of malignancy. Although various abnormalities in T cell function of HD patients have been described, it remains unclear whether this is due to an intrinsic T cell defect. Aim: In the present study we tested the capacity of T cells to proliferate upon stimulation with antigen-presenting cell and T-cell-derived cytokines. Methods: The proliferation capacity of lymphocytes obtained from patients on HD and healthy controls was determined by measuring the proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with rhIL-2, rhIL-15, rhTNF-α, or combination of those cytokines. In all samples the percentage of α/β TCR-positive T cells was measured. Results: After isolation of PBMC the percentage of T cells varied from 70% (before stimulation) to 80% (after stimulation). IL-2, IL-15 and TNF-α all induced PBMC proliferation, while the combination TNF-α plus IL-2 or TNF-α plus IL-15 appeared to be additive. No difference between PBMC from HD patients and controls was found. Conclusion: We conclude that lymphocytes from HD patients have no intrinsic defects in their proliferation capacity after stimulation with IL-2, IL-15 or TNF-α, in vitro, as the increase in counts per minute is predominant.

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          Most cited references 3

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          Interleukin 15: a proinflammatory role in rheumatoid arthritis synovitis.

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            T cells activate the tumor necrosis factor-alpha system during hemodialysis, resulting in tachyphylaxis.

            The immunosuppressive state of hemodialysis (HD) patients is accompanied by activation of antigen-presenting cell-derived cytokines, for example, tumor necrosis factor-alpha (TNF-alpha), which are required for T-cell activation. To test whether an activated TNF-alpha system results in impaired T-cell response in these patients, we analyzed parameters of their antigen-presenting cell (APC) function (for example, TNF-alpha system) and T-cell function [for example, interleukin-2 (IL-2) system]. By quantitative flow cytometry, the expression of the TNF-receptor 2 (TNF-R2 = CD120b) and the alpha and beta chain of the IL-2 receptor (IL-2R; CD25, CD122) was measured. Using reverse transcriptase-polymerase chain reaction, the mRNA for TNF-alpha, IL-2, and IL-2R were determined. Phyto-hemagglutinin (PHA)- and IL-2-stimulated proliferation and cytokine production were measured. Biological activity of soluble receptors was measured by adding recombinant cytokines to the patient's plasma. CD120b expression was significantly increased in HD patients, whereas CD25 and CD122 was comparable to controls. In contrast to mRNA for IL-2 and IL-2R, mRNA for TNF-alpha was increased in HD. This resulted in significantly increased TNF-alpha levels in HD patients. In peripheral blood of HD patients, high levels of soluble TNF-R (R1 and R2) and IL-2R were found. These receptors were capable of binding 40% of added TNF-alpha and 55% of added IL-2. PHA-induced TNF-alpha production by T cells from HD patients was significantly lower, while their PHA-stimulated IL-2 production and proliferation capacity by T cells were comparable to controls. We conclude that although the TNF-alpha system is activated during HD, the TNF-alpha production of T cells is impaired, suggesting that tachyphylaxis of T cells occurs for TNF-alpha, as their proliferative capacity and IL-2 production capacity do not imply an intrinsic T-cell defect.
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              The macrophage-derived T-Cell growth factor interleukin-15 is present in interleukin-2–independent rejection after clinical heart and liver transplantation

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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2003
                2003
                26 February 2003
                : 21
                : 2
                : 158-162
                Affiliations
                Department of Internal Medicine, Erasmus University Medical Center Rotterdam, The Netherlands
                Article
                69154 Blood Purif 2003;21:158–162
                10.1159/000069154
                12601258
                © 2003 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, References: 31, Pages: 5
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/69154
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