DARWIN Digitale Dissertationen German Version Strich

FU Berlin
Digitale Dissertation

Anne-Christine Karow :
Immunohistochemical Findings on the Influence of Immunosuppressive Therapy after Penetrating Keratoplasty in the Rat
Immunhistochemische Befunde zum Einfluß immunsuppressiver Therapie nach perforierender Keratoplastik am Rattenauge

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|Abstract| |Table of Contents| |More Information|

Abstract

Utilising immunohistochemistry it has been investigated which cells of the immune system in which proportion to each other and in which timely sequence are infiltrating the graft after penetrating keratoplasty in the rat eye. After transplantation the rats had been treated with different immunosuppressing or tolerogenic agents. The rat strains used as donor and recipient are different in their MHC antigens so that transplantation in untreated animals always leads to allograft rejection.

Blocking the CD4 antigen expressed on T-helper cells by treating the animals with the monoclonal anti-CD4 antibody RIB 5/2 leads to much less infiltration of the graft by all cell populations investigated. This is probably due to the increased secretion of Th2-cytokines by T-helper cells on antigen recognition after blocking the CD4-molecule. Th2-cytokines are immunosuppressing in the context of allograft rejection.

This is corresponding to the clinical observation that most of the animals treated with the anti-CD4 antibody are not rejecting their graft.

Treatment with Leflunomide or with Cyclosporine remained without effect in this setting.

These results support the view that CD4+ T-cells although not destroying the infiltrated tissue themselves are of central importance in allograft rejection because of their initialising role and that blocking normal T-cell function may interrupt allograft reaction in the cornea.

Treatment with anti-CD4 antibodies seems to be a promising alternative in preventing allograft rejection after penetrating keratoplasty.


Table of Contents

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EINLEITUNG

6

1. Hornhauttransplantation

6

2. Die Pathogenese der Abstossungsreaktion

8

3. Makropathologie und Histologie der Transplantatabstossung

16

4. Prävention und Behandlung der Abstossung in der Klinik

17

5. Tiermodelle ? Kaninchen, Ratte, Maus

18

6. Experimentelle Therapieformen

20

7. Fragestellung

28

MATERIAL UND METHODEN

29

ERGEBNISSE

38

1. Aus der Studie ausgeschlossene Tiere

38

2. Normale (nicht operierte) Rattenaugen

38

3. Hornhauttransplantierte Augen

38

DISKUSSION

54

ZUSAMMENFASSUNG

71

ANHANG

72

LITERATURVERZEICHNIS

75


More Information:

Online available: http://www.diss.fu-berlin.de/2001/164/indexe.html
Language of PhDThesis: german
Keywords: Keratoplasty, Immunosuppression, Immunohistochemistry, Monoclonal Anti-CD4-Antibodies, Allograft Reaction
DNB-Sachgruppe: 33 Medizin
Date of disputation: 21-May-2001
PhDThesis from: Fachbereich Humanmedizin, Freie Universität Berlin
First Referee: Prof. Dr. med. Friedrich Hoffmann
Second Referee: Prof. Dr. med. Michael Wiederholt
Contact (Author): anne.karow@berlin.de
Contact (Advisor): fhoffman@zedat.fu-berlin.de
Date created:31-Aug-2001
Date available:31-Aug-2001

 


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