Stability and plasticity of T helper type 1 and type 2 differentiation programs:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Berlin
Mensch und Buch Verl.
2012
|
| Schriftenreihe: | Biological science
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | IX, 140 S. Ill., graph. Darst. |
| ISBN: | 9783863871925 |
Internformat
MARC
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| 100 | 1 | |a Hegazy, Ahmed Nabil |d 1978- |e Verfasser |0 (DE-588)143698575 |4 aut | |
| 245 | 1 | 0 | |a Stability and plasticity of T helper type 1 and type 2 differentiation programs |c von Ahmed Nabil Hegazy |
| 264 | 1 | |a Berlin |b Mensch und Buch Verl. |c 2012 | |
| 300 | |a IX, 140 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
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| 502 | |a Zugl.: Berlin, Humboldt-Univ., Diss., 2012 | ||
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Datensatz im Suchindex
| _version_ | 1804149434653605888 |
|---|---|
| adam_text | IMAGE 1
TABLE OF CONTENTS
ZUSAMMENFASSUNG I
ABSTRACT III
1 INTRODUCTION 1
1.1 THE IMMUNE SYSTEM 1
1.2 C D 4 + T CELL DIFFERENTIATION PROGRAMS 1
1.3 CYTOKINE SIGNALLING IN THL/TH2 CELL DIFFERENTIATION 4
1.3.1 SIGNALLING PATHWAY IN T H L CELL DEVELOPMENT 5
1.3.2 SIGNALLING PATHWAY IN TH2 CELL DEVELOPMENT 7
1.4 TRANSCRIPTION FACTORS GUIDING THL/TH2 CELL DIFFERENTIATION 10
1.4.1 TRANSCRIPTION FACTORS GUIDING T H L CELL DIFFERENTIATION 10
1.4.2 TRANSCRIPTION FACTORS GUIDING TH2 CELL DIFFERENTIATION 12
1.5 CYTOKINE MEMORY AND MAINTENANCE 14
1.6 PLASTICITY O F C D 4 + T CELL SUBSETS 15
1.6.1 STABILITY AND PLASTICITY O F THE T H L DIFFERENTIATION PROGRAM 16
1.6.2 STABILITY AND PLASTICITY O F THE TH2 DIFFERENTIATION PROGRAM 21
1.7 MEMORY CD4 + T CELL DIFFERENTIATION PATHWAYS 23
1.8 ROLE O F CD4 + T CELL SUBSETS IN ORCHESTRATING THE IMMUNE RESPONSE
24
1.8.1 C D 4 + T CELLS IN ANTIVIRAL IMMUNE REPONSES 26
1.8.1.1 EFFECTOR C D 4 + T CELL SUBSETS IN VIRAL INFECTIONS 26
1.8.1.2 ROLE O F CD4 + T CELLS DURING VIRAL INFECTIONS 27
1.9 A I M OF THE STUDY 29
2 RESULTS 30
2.1 LONG-LIVED VIRUS-REACTIVE CD4 + M E M O R Y T CELLS EMERGE FROM
EFFECTOR
T CELLS 3 0
2.1.1 GENERATION O F MEMORY T CELLS FROM LONG-TERM DIFFERENTIATED T H L
AND TH2 EFFECTORS V 30
2.1.2 GENERATION O F EFFECTOR MEMORY T CELLS FROM PURIFIED
IFN-Y-SECRETING
EFFECTORS PRIMED IN VIVO 31
2.1.3 T H L AND TH2 EFFECTOR-DERIVED MEMORY CELLS MAINTAIN PREFERENTIAL
PRODUCTION O F KEY TRANSCRIPTION FACTORS AND CYTOKINES 33
IV
HTTP://D-NB.INFO/1025398289
IMAGE 2
C O N T E N T
2.1.4 FUNCTIONAL REACTIVITY O F T H L AND TH2 EFFECTOR-DERIVED MEMORY
CELLS
UPON VIRUS CHALLENGE 35
2.2 STABILITY AND PLASTICITY O F IN V/VO-DIFFERENTIATED T H L CELLS 38
2.2.1 LCMV INFECTION DRIVES STRONG T H L CELL DIFFERENTIATION AND STABLE
T-BET INDUCTION 38
2.2.2 IL-4-MEDIATED GATA-3 INDUCTION IN IN V/VO-PRIMED T H L CELLS 4 0
2.2.3 LONG-TERM MAINTENANCE O F IL-4-INDUCED T-BET HL8H GATA-3 11
T H L + 2 P H E N O T Y P E 4 5
2.2.4 TYPE I AND TYPE II INTERFERONS AND T-BET STABILIZE VIRUS-SPECIFIC
T H L CELLS 46
2.2.5 INTERMEDIATE T-BET PROTEIN AMOUNTS IN TBX21 +/~ T H L CELLS PERMIT
ENHANCED
GATA-3 INDUCTION 48
2.2.6 GRADED T-BET EXPRESSION GOVERNS THL CELL PLASTICITY 50
2.2.7 IFN-Y EXPRESSION MAGNITUDE PREDICTS T H L CELL PLASTICITY 53
2.3 STABILITY AND PLASTICITY O F TH2-COMMITTED T CELLS IN THE CONTEXT OF
VIRAL INFECTIONS 57
2.3.1 TH2 CELLS RESIST REPROGRAMMING TOWARD T H L CELLS BY 1L-12 AND
IFN-Y 57
2.3.2 VIRUS INFECTIONS REVEAL PLASTICITY O F TH2 CELLS IN THE CONTEXT OF
SPECIFIC TCR-STIMULATION 57
2.3.3 VIRUS-DRIVEN TH2 CELL REPROGRAMMING REQUIRES INDUCTION O F T-BET
59
2.3.4 LONG-TERM MAINTENANCE O F THE VIRUS-INDUCED GATA-3 +T-BET+
AND IL-4+IFN-Y+ T H 2 + 1 PHENOTYPE IN VIVO 62
2.3.5 TYPE I AND TYPE II INTERFERONS AND IL-12 ARE ESSENTIAL FOR
VIRUS-INDUCED
TH2 CELL REPROGRAMMING 63
2.3.6 INTERFERONS AND IL-12 COOPERATE IN INDUCTION O F T-BET AND IFN-Y
IN TH2 CELLS IN VITRO 67
2.3.7 T-BET INDUCTION IN ADOPTIVELY TRANSFERRED VIRUS-SPECIFIC TH2 CELLS
IS
CRUCIAL TO PREVENT L C M V PERSISTENCE AND FATAL IMMUNOPATHOLOGY 69
3 DISCUSSION 73
3.1 PATHWAYS O F MEMORY CD4 + T CELL DIFFERENTIATION 73
3.1.1 EFFECTOR TO MEMORY TRANSITION O F CD4 + T CELLS 74
3.1.2 LONG-TERM STABILITY O F T CELL DIFFERENTIATION PROGRAMS 77
3.1.3 CONCLUSION AND OUTLOOK 78
V
IMAGE 3
C O N T E N T
3.2 STABILITY AND PLASTICITY O F IN V/VO-DIFFERENTIATED T H L CELLS 80
3.2.1 IN VITRO- VERSUS IN V/VO-PRIMED T H L CELLS 81
3.2.2 IL-4 RESPONSIVNESS AND GATA-3 UP-REGULATION IN T H L CELLS 82
3.2.3 INTERFERONS STABILIZE THE T H L CELL PHENOTYPE 84
3.2.4 DIFFERENTIAL UP-REGULATION O F GATA-3 IN T H L CELLS 85
3.2.5 IFN-Y EXPRESSION MAGNITUDE AND LY6C EXPRESSION MARK FLEXIBLE T H L
CELLS 86
3.2.6 CONCLUSION AND OUTLOOK 87
3.3 INTERFERONS AND THE TRANSCRIPTION FACTOR T-BET REGULATE T HELPER 2
CELL
PLASTICITY 89
3.3.1 CYTOKINE SIGNALS ENFORCING THE TH2 CELL REPROGRAMMING 90
3.3.1.1 TYPE I INTERFERONS 90
3.3.1.2 INTERFERON-Y 91
3.3.1.3 INTERLEUKIN-12 92
3.3.2 TYPE I AND TYPE II INTERFERON SIGNALLING CROSS-TALK PROMOTES
TH2 CELL REPROGRAMMING 93
3.3.3 T-BET-DEPENDENT IFN-Y INDUCTION AND TH2 CELL REPROGRAMMING 94
3.3.4 TH2-MEDIATED C D 8 + T CELL SUPPRESSION AND IMMUNOPATHOLOGY 97
3.3.5 CONCLUSION AND OUTLOOK 98
4 MATERIALS AND METHODS 100
4.1 MICE 100
4.2 LYMPHOCYTIC CHORIOMENINGITIS VIRUS MODEL 100
4.2.1 VIRUSES 102
4.2.2 L C M V PLAQUE-FORMING ASSAY 102
4.3 CELL LINES 103
4.4 MAGNETIC CELL SORTING 103
4.5 T CELL ACTIVATION AND DIFFERENTIATION 104
4.6 ADOPTIVE T CELL TRANSFER 105
4.7 CYTOKINE SECRETION ASSAY 106
4.8 FLOW CYTOMETRY AND CELL SORTING 108
4.9 INTRACELLULAR CYTOKINE STAINING 108
4.10 TETRAMER STAINING 109
4.11 TRANSCRIPTION FACTORS STAINING 109
4.12 INTRACELLULAR STAT PROTEIN STAINING 109
VI
IMAGE 4
C O N T E N T
4.13 CYTOKINE ANALYSIS IN SERA AND SUPERNATANTS 110
4.14 CALCULATION O F THE HALF-LIFE 110
4.15 STATISTICAL ANALYSIS 111
5 REFERENCES 112
6 APPENDIX 136
CURRICULUM VITAE 134
PUBLICATIONS 136
ACKNOWLEDGMENTS 139
SELBSTANDIGKEITSERKLARUNG 140
VII
|
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| dewey-ones | 571 - Physiology & related subjects |
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| dewey-search | 571.966 |
| dewey-sort | 3571.966 |
| dewey-tens | 570 - Biology |
| discipline | Biologie |
| format | Thesis Book |
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| spelling | Hegazy, Ahmed Nabil 1978- Verfasser (DE-588)143698575 aut Stability and plasticity of T helper type 1 and type 2 differentiation programs von Ahmed Nabil Hegazy Berlin Mensch und Buch Verl. 2012 IX, 140 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Biological science Zugl.: Berlin, Humboldt-Univ., Diss., 2012 Zelldifferenzierung (DE-588)4067536-1 gnd rswk-swf Helferzelle (DE-588)4258130-8 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Helferzelle (DE-588)4258130-8 s Zelldifferenzierung (DE-588)4067536-1 s DE-604 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025242599&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Hegazy, Ahmed Nabil 1978- Stability and plasticity of T helper type 1 and type 2 differentiation programs Zelldifferenzierung (DE-588)4067536-1 gnd Helferzelle (DE-588)4258130-8 gnd |
| subject_GND | (DE-588)4067536-1 (DE-588)4258130-8 (DE-588)4113937-9 |
| title | Stability and plasticity of T helper type 1 and type 2 differentiation programs |
| title_auth | Stability and plasticity of T helper type 1 and type 2 differentiation programs |
| title_exact_search | Stability and plasticity of T helper type 1 and type 2 differentiation programs |
| title_full | Stability and plasticity of T helper type 1 and type 2 differentiation programs von Ahmed Nabil Hegazy |
| title_fullStr | Stability and plasticity of T helper type 1 and type 2 differentiation programs von Ahmed Nabil Hegazy |
| title_full_unstemmed | Stability and plasticity of T helper type 1 and type 2 differentiation programs von Ahmed Nabil Hegazy |
| title_short | Stability and plasticity of T helper type 1 and type 2 differentiation programs |
| title_sort | stability and plasticity of t helper type 1 and type 2 differentiation programs |
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