B7-1 (CD80) and B7-2 (CD 86) Expression in Human Tubular Epithelial Cells in vivo and in vitro<footref rid="foot01"> ¹</footref>

Abstract

Background: Tubulointerstitial inflammation with infiltration of mononuclear cells plays an important role in acute allograft rejection and in the progression of renal diseases. We therefore investigated in vivo the expression of the costimulatory molecules B7-1 and B7-2 on proximal tubular epithelial cells (PTEC) under normal and pathologic conditions and analyzed the regulation and functional role of these molecules after cytokine and CD40 activation in vitro. Methods: Immunohistological staining for B7-1 and B7-2 on cryostat sections of core needle biopsies from patients with different renal diseases was examined. Patients were divided into three groups: group A: diffuse interstitial inflammation; group B: minor interstitial inflammation; group C: no interstitial inflammation. In addition, the expression of B7-1 and B7-2 protein and mRNA of cultured PTEC that had been stimulated with cytokine-combinations in absence or presence of a stimulatory anti-CD40 antibody was investigated by means of FACS analysis and RT-PCR. The functional role was analyzed in MKLCs with cytokine and anti-CD40 prestimulated PTEC by measuring IFN-γ and IL-2 expression in absence or presence of CTLA4-Ig by ELISA. Results: Group A patients showed intense tubular staining for B7-1 and B7-2, group B patients showed mild staining, whereas in group C patients B7-1 and B7-2 staining was negative or only weakly positive. In vitro, the presence of B7-1 and B7-2 on PTEC was increased after stimulation with combinations of IL-1α, IL-4, IFN-γ or IL-13 instead of IL-4 and CD40 activation. B7-1 and B7-2 mRNA could be detected in PTEC as well. In MKLCs only cytokine and anti-CD40 prestimulated PTEC were able to stimulate IFN-γ and IL-2 production by purified T cells, which could be blocked dose-dependently by CTLA4-Ig. Conclusion: This study clearly shows that B7-1 and B7-2 can be induced on PTEC in vivo and in vitro. After B7-1 and B7-2 induction, PTEC costimulate CD28 on T lymphocytes resulting in cytokine production. This might be of relevance in allograft rejection and in various kidney diseases.

Journal

Journal ID (publisher-id): NEF

Journal ID (nlm-ta): Nephron

Journal ID (doi): 10.1159/issn.1660-8151

Title: Nephron

Publisher: S. Karger AG

ISSN (Print): 1660-8151

ISSN (Electronic): 2235-3186

Publication date Subscription-year: 2002

Publication date (Print): September 2002

Publication date (Electronic): 26 September 2002

Volume: 92

Issue: 3

Pages: 542-556

Affiliations

^aVth Medical Clinic, Klinikum Mannheim, Ruprecht-Karls University of Heidelberg at Mannheim, and ^bInstitute of Pathology, Heidelberg, Germany

Article

Publisher ID: 64084 Other ID: Nephron 2002;92:542–556

DOI: 10.1159/000064084

PubMed ID: 12372936

Copyright statement: © 2002 S. Karger AG, Basel

License:

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: 10, Tables: 2, References: 60, Pages: 15

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Categories

Subject: Original Paper