Quantitative cytokine memory of T helper cells:
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
2013
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | 112 S. Ill., graph. Darst. |
Staff View
MARC
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| 100 | 1 | |a Helmstetter, Caroline |d 1981- |e Verfasser |0 (DE-588)1042618720 |4 aut | |
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Record in the Search Index
| _version_ | 1804151416967659520 |
|---|---|
| adam_text | CONTENTS
1 INTRODUCTION 12
1.1 THE IMMUNE SYSTEM 12
1.2 ADAPTIVE IMMUNITY 12
1.3 GENERATION OF EFFECTOR AND MEMORY TH CELLS 13
1.4 ACTIVATION OF NAIVE AND EFFECTOR TH CELLS BY TCR SIGNALING 14
1.5 DIFFERENTIATION OF T HELPER CELLS INTO SPECIALIZED SUBSETS 15
1.5.1 DIFFERENTIATION OF THL CELLS 15
1.5.2 DIFFERENTIATION OF TH2 CELLS 17
1.5.3 DIFFERENTIATION OF THL7 CELLS AND INDUCED REGULATORY T CELLS ....
18
1.5.4 DIFFERENTIATION OF FURTHER TH CELL LINEAGES 19
1.6 PLASTICITY IN TH CELL DIFFERENTIATION AND GENERATION OF HYBRID TH
CELL PHE-
NOTYPES 20
1.7 CYTOKINE PRODUCTION BY TH CELLS 20
1.7.1 CHARACTERISTICS OF CYTOKINE EFFECTOR FUNCTIONS 21
1.7.2 CYTOKINE SIGNALING 21
1.7.3 CYTOKINE PRODUCTION DURING TH CELL DIFFERENTIATION AND CYTOKINE
MEMORY 22
1.7.4 THE IFNG LOCUS AND ITS REMODELING DURING THL CELL DIFFERENTIATION
. 24
1.7.5 ALLELIC CONTRIBUTIONS TO CYTOKINE EXPRESSION 26
1.7.6 HETEROGENEITY OF CYTOKINE GENE EXPRESSION 26
1.8 EXPERIMENTAL MODELS TO STUDY TH CELL DIFFERENTIATION AND FUNCTION
.... 27
1.8.1 LCMV INFECTIONS ARE A CLASSIC MODEL FOR THL CELL DIFFERENTIATION
IN
VIVO 27
1.8.2 H. POLYGYRUS INFECTIONS ARE A CLASSIC MODEL FOR TH2 CELL
DIFFERENTI
ATION IN VIVO 28
1.9 AIMS OF THE STUDY 29
2 RESULTS 30
2.1 EFFECTOR TH CELLS SEGREGATE INTO STABLE CYTOKINE-PRODUCING AND
-NONPRODUCING
SUBSETS 30
2.1.1 EFFECTOR CYTOKINE PRODUCTION IS HETEROGENEOUS IN POPULATIONS OF
DIFFERENTIATED THL, TH2, AND THL7 CELLS 30
2.1.2 EFFECTOR CYTOKINES ARE PRODUCED BY A STABLE SUBPOPULATION OF ACTI
VATED TH CELLS 31
2.2 INDIVIDUAL TH CELLS STABLY COMMIT TO A SPECIFIC LEVEL OF EFFECTOR
CYTOKINE
PRODUCTION 37
HTTP://D-NB.INFO/1044765704
CONTENTS
2.3 INDIVIDUAL THL CELLS HAVE A QUALITATIVE AND QUANTITATIVE MEMORY FOR
IFN-Y
EXPRESSION 41
2.3.1 IN MTRO-GENERATED THL CELLS MEMORIZE THEIR SPECIFIC RATES OF IFN-Y
AND T-BET EXPRESSION 41
2.3.2 THE QUANTITATIVE MEMORY FOR IFN-Y PRODUCTION IS REGULATED AT THE
LEVEL OF TRANSCRIPTION .... . 42
2.3.3 IN MUODIFFERENTIATED VIRUS-SPECIFIC THL CELLS EXHIBIT A
QUANTITATIVE
MEMORY FOR IFN-Y AND T-BET EXPRESSION 45
2.3.4 DISTINCT IFN-Y EXPRESSION LEVELS ARE PROPERTIES OF BONA FIDE THL
CELLS 46
2.4 T-BET EXPRESSION LEVELS ARE PREDICTIVE OF THE IFN-Y CYTOKINE MEMORY
... 50
2.4.1 T-BET-ZSGREEN REPORTER MICE RELIABLY PERMIT ACCESS TO VIABLE THL
CELLS THAT EXPRESS T-BET AT DISTINCT LEVELS 50
2.4.2 THL CELLS EXHIBIT A LONG-TERM QUANTITATIVE MEMORY FOR IFN-Y IN
VIVO, DETERMINED BY THEIR EARLIER EXPRESSION OF T-BET 51
2.5 QUANTITATIVE MODULATIONS OF CYTOKINE EXPRESSION IN HYBRID THL/2
CELLS . . 56
2.5.1 LOWER T-BET AMOUNTS CORRELATE WITH REDUCED IFN-Y EXPRESSION IN
HYBRID THL/2 CELLS IN VITRO 56
2.5.2 HYBRID THL/2 CELLS ARE LESS PATHOGENIC THAN CONVENTIONAL THL CELLS
IN A TYPE-1 INFLAMMATION MODEL 57
2.5.3 HYBRID THL/2 CELLS CAUSE MILDER IMMUNOPATHOLOGY THAN CONVEN
TIONAL TH2 CELLS IN A TYPE-2 AIRWAY INFLAMMATION 58
2.5.4 HYBRID THL/2 CELLS DEVELOP IN IMMUNE RESPONSES AGAINST HELMINTHS
61
3 DISCUSSION 63
3.1 COMMITMENT OF INDIVIDUAL T CELLS TO STABLE LEVELS OF CYTOKINE
EXPRESSION . 63
3.1.1 STABLE CELLULAR DECISIONS ARE THE BASIS OF HETEROGENEOUS CYTOKINE
PRODUCTION 64
3.1.2 INDIVIDUAL ACTIVATED TH CELLS PRODUCE DISTINCT AMOUNTS OF
CYTOKINES
THROUGHOUT A STIMULATION PERIOD 65
3.2 QUANTITATIVE CYTOKINE MEMORY OF TH CELLS 66
3.2.1 IFN-Y MEMORY IS REFLECTED IN PROBABILITY AND AMOUNT OF
REEXPRESSION 66
3.2.2 IFN-Y MEMORY CORRELATES WITH T-BET EXPRESSION LEVELS 68
3.2.3 T-BET AMOUNTS ARE PREDICTIVE OF IFN-Y REEXPRESSION 70
3.2.4 THE QUANTITATIVE IFN-Y MEMORY IS REGULATED AT THE LEVEL OF TRAN
SCRIPTION 71
3.2.5 MOLECULAR BASIS FOR IFN-Y CYTOKINE MEMORY 73
3.3 DEFINING EFFECTOR THL CELLS - ARE ONLY ACUTE IFN-Y-PRODUCERS TRUE
EFFECTORS? 78
3.4 FUNCTIONAL RELEVANCE OF CYTOKINE EXPRESSION LEVELS *. 79
3.4.1 FUNCTIONAL BEHAVIOR OF THL CELLS SORTED FOR IFN-Y LEVELS 79
3.4.2 FUNCTIONAL RELEVANCE OF HYBRID THL/2 CELLS WITH MODULATED CYTO
KINE EXPRESSION 80
3.5 CONCLUSION 82
CONTENTS
4 MATERIALS AND METHODS 83
4.1 MICE 83
4.2 ADOPTIVE CELL TRANSFER 83
4.3 VIRUSES AND PARASITES 83
4.4 INFECTIONS AND IMMUNIZATIONS 84
4.5 AIRWAY INFLAMMATION MODEL 84
4.6 HISTOLOGY 84
4.7 ISOLATION OF NAIVE TH CELLS 84
4.8 CELL ISOLATION AND FLOW CYTOMETRY 85
4.9 PRIMARY T CELL CULTURES 86
4.10 INTRACELLULAR CYTOKINE STAINING 86
4.11 TRANSCRIPTION FACTOR STAINING 87
4.12 CYTOKINE SECRETION ASSAY 87
4.13 REAL-TIME PCR 88
4.14 STATISTICAL ANALYSIS 89
4.15 MATHEMATICAL MODELING 89
5 APPENDIX 108
5.1 COOPERATION PARTNERS 108
5.2 ACKNOWLEDGEMENTS 109
5.3 SELBSTANDIGKEITSERKLARUNG 110
5.4 PUBLICATIONS ILL
5.5 SCIENTIFIC PRESENTATIONS AND SCHOLARSHIPS ILL
5.6 CURRICULUM VITAE 112
|
| any_adam_object | 1 |
| author | Helmstetter, Caroline 1981- |
| author_GND | (DE-588)1042618720 |
| author_facet | Helmstetter, Caroline 1981- |
| author_role | aut |
| author_sort | Helmstetter, Caroline 1981- |
| author_variant | c h ch |
| building | Verbundindex |
| bvnumber | BV041342834 |
| classification_rvk | WF 9895 |
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| dewey-full | 610 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 610 - Medicine and health |
| dewey-raw | 610 |
| dewey-search | 610 |
| dewey-sort | 3610 |
| dewey-tens | 610 - Medicine and health |
| discipline | Biologie Medizin |
| format | Thesis Book |
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| indexdate | 2024-07-10T00:54:29Z |
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| language | English |
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| physical | 112 S. Ill., graph. Darst. |
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| spelling | Helmstetter, Caroline 1981- Verfasser (DE-588)1042618720 aut Quantitative cytokine memory of T helper cells von Caroline Helmstetter 2013 112 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Berlin, Humboldt-Univ., Diss., 2013 T-Lymphozyt (DE-588)4127387-4 gnd rswk-swf Cytokine (DE-588)4205701-2 gnd rswk-swf Immunreaktion (DE-588)4133841-8 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content T-Lymphozyt (DE-588)4127387-4 s Cytokine (DE-588)4205701-2 s Immunreaktion (DE-588)4133841-8 s 1\p DE-604 Reproduziert als Helmstetter, Caroline Quantitative cytokine memory of T helper cells Berlin : MIK-Center GmbH, 2013 2 Mikrofiches (DE-604)BV041710008 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026791570&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Helmstetter, Caroline 1981- Quantitative cytokine memory of T helper cells T-Lymphozyt (DE-588)4127387-4 gnd Cytokine (DE-588)4205701-2 gnd Immunreaktion (DE-588)4133841-8 gnd |
| subject_GND | (DE-588)4127387-4 (DE-588)4205701-2 (DE-588)4133841-8 (DE-588)4113937-9 |
| title | Quantitative cytokine memory of T helper cells |
| title_auth | Quantitative cytokine memory of T helper cells |
| title_exact_search | Quantitative cytokine memory of T helper cells |
| title_full | Quantitative cytokine memory of T helper cells von Caroline Helmstetter |
| title_fullStr | Quantitative cytokine memory of T helper cells von Caroline Helmstetter |
| title_full_unstemmed | Quantitative cytokine memory of T helper cells von Caroline Helmstetter |
| title_short | Quantitative cytokine memory of T helper cells |
| title_sort | quantitative cytokine memory of t helper cells |
| topic | T-Lymphozyt (DE-588)4127387-4 gnd Cytokine (DE-588)4205701-2 gnd Immunreaktion (DE-588)4133841-8 gnd |
| topic_facet | T-Lymphozyt Cytokine Immunreaktion Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026791570&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT helmstettercaroline quantitativecytokinememoryofthelpercells |