Cover Page The handle http://hdl.handle.net/1887/38020 holds various files of this Leiden University dissertation.

Cover Page

The handle http://hdl.handle.net/1887/38020 holds various files of this Leiden University dissertation.

Author: Welten, Suzanne Petronella Maria

Title: Tuning virus-specific T cell responses by costimulatory signals

Issue Date: 2016-02-18

TUNING VIRUS-SPECIFIC T CELL RESPONSES BY COSTIMULATORY

SIGNALS

Suzanne Petronella Maria Welten

Promotores:

Prof. dr. C. J. M. Melief Prof. dr. F. Ossendorp Co-promotor:

Dr. R. Arens

Leden promotiecommissie:

Prof. dr. J. Borst

(Universiteit van Amsterdam, NKI, Amsterdam) Prof. dr. R. A. W. van Lier

(Universiteit van Amsterdam, Sanquin, Amsterdam) Prof. dr. T. H. M. Ottenhoff

Dr. M. E. Ressing

The research described in this thesis was performed at the Department of Immunohematology and Blood Transfusion of the Leiden University Medical Center, Leiden, The Netherlands and was supported by a Marie Curie Fellowship  from the  European Commission  and a Gisela Thier grant from the  Leiden University Medical Center. Financial support for the publication of this thesis was provided by the Leiden University Medical Center and Synvolux, Leiden, The Netherlands.

Cover & layout: Michel Counotte and Suzanne Welten

ISBN: 978-94-028-0031-9

TUNING VIRUS-SPECIFIC T CELL RESPONSES BY COSTIMULATORY

SIGNALS

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,

volgens besluit van College voor Promoties te verdedigen op donderdag 18 februari 2016

klokke 13:45 uur door

Suzanne Petronella Maria Welten

geboren te Roosendaal in 1986

TABLE OF CONTENTS:

Chapter 1 General introduction 6

Chapter 2 The distinct role of T cell costimulation in antiviral immunity 14 Chapter 3 Memory T cell inflation: understanding cause and effect 26

Chapter 4 CD27-CD70 costimulation control T cell immunity during 40 acute and persistent Cytomegalovirus infection

*Appendix: Interfering with CD70-mediated costimulation: 64 a putative immune evasion mechanism by mouse cytomegalovirus

Chapter 5 Viral inoculum dose impacts memory T cell inflation 66

Chapter 6 Viral persistence induces antibody inflation deprived of altering 82 antibody avidity

Chapter 7 The quantity of autocrine IL-2 governs the expansion potential 98 of CD8

T cells

Chapter 8 CD70- and CD80/86-mediated costimulatory pathways collectively 118 program CD8

T cells for autocrine IL-2 production

Chapter 9 The viral context instruct the redundancy of costimulatory 142 pathways in driving CD8

T cell expansion

Chapter 10 Discussion 170

English summary 182

Nederlandse samenvatting 184

Curriculum Vitae 186

List of Publications 187

Acknowledgements 188