Dynamics of Regulatory T cells in Liver Transplantation Ahmet Demirkiran Page 2 The studies ...

153 Pages·2007·4.22 MB·Dutch

Dynamics of Regulatory T cells
in Liver Transplantation
Ahmet Demirkiran
The studies described in this thesis were performed at the Department of Surgery,
Erasmus MC, Rotterdam, the Netherlands.
Financial support for this research was provided by a Revolving Fund from the Erasmus MC and
a Gastrostart grant from the Dutch Society of Gastroenterology and Hepatology
Financial support for the publication of this thesis was kindly provided by Roche Nederland B.V.,
Novartis Pharma B.V., Wyeth, C & E Bankiers, Merck Sharpe & Dohme, Tyco Healthcare B.V.,
Stichting Lever Onderzoek, Nederlandse Transplantatie Vereniging, Genzyme en Astellas Pharma B.V.,
producent van o.a. Advagraf en Prograft
Cover design by Elwin J. Bes
Lay-out design by Ayhan Beyazıt
Printed by Optima Grafische Communicatie, Rotterdam
ISBN 978-90-8559-323-2
© Ahmet Demirkiran, Rotterdam, 2007
Dynamics of Regulatory T cells in Liver Transplantation
Dynamiek van Regulatoire T cellen in Levertransplantatie
Proefschrift
ter verkrijging van de graad van doctor aan de
Erasmus Universiteit Rotterdam
op gezag van de
rector magnificus
Prof.dr. S.W.J. Lamberts
en volgens besluit van de College voor Promoties
De openbare verdediging zal plaatsvinden op
woensdag 28 november 2007 om 13:45 uur
door
Ahmet Demirkiran
geboren te Rotterdam
PROMOTIECOMMISSIE
Promotor: Prof.dr. H.W. Tilanus
Overige Leden: Prof.dr. J.N.M. Ijzermans
Prof.dr. W. Weimar
Prof.dr. J.D. Laman

Copromotor: Dr. L.J.W. van der Laan
CONTENTS
Part I General introduction
Chapter 1 Introduction and outline 9
Chapter 2 Impact of immunosuppressive drugs on CD4+CD25+Foxp3+ 19
regulatory T cells: Does in vitro evidence translate to the
clinical setting?
Part II Regulatory T cells in peripheral blood
Chapter 3 Decrease of CD4+CD25+ T cells in peripheral blood after liver 37
transplantation: association with immune suppression
Chapter 4 Low circulating regulatory T-cell levels after acute rejection in 45
liver transplantation
Chapter 5 Changes of circulating CD4+Foxp3+ regulatory T cells after 61
conversion from calcineurin inhibitor to mycophenolate mofetil
in liver transplantation
Part III Regulatory T cells in the liver
Chapter 6 Allo-suppressive donor CD4+CD25+ regulatory T cells detach 79
from the liver graft and circulate in recipients after liver
transplantation
Chapter 7 Low IL-10 gene expression levels in liver and blood during 97
acute rejection after liver transplantation
Chapter 8 Intrahepatic detection of Foxp3 gene expression after liver 111
transplantation using minimally invasive aspiration biopsy
Part IV Closure
Chapter 9 Summary and discussion 123
Chapter 10 Dutch summary (Samenvatting) 135
Appendix Acknowledgements (Dankwoord) 145
Curriculum Vitae Auctoris 149
List of publications 151

Part I

General introduction

Chapter 1
Introduction and outline