Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2015
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XXII, 176 S. Ill., graph. Darst. |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV043012252 | ||
| 003 | DE-604 | ||
| 005 | 00000000000000.0 | ||
| 007 | t | ||
| 008 | 151117s2015 ad|| m||| 00||| eng d | ||
| 035 | |a (OCoLC)935114448 | ||
| 035 | |a (DE-599)BVBBV043012252 | ||
| 040 | |a DE-604 |b ger |e rakwb | ||
| 041 | 0 | |a eng | |
| 049 | |a DE-83 |a DE-91 | ||
| 100 | 1 | |a Maschmeyer, Patrick |e Verfasser |0 (DE-588)107892547X |4 aut | |
| 245 | 1 | 0 | |a Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes |c vorgelegt von Patrick Maschmeyer |
| 246 | 1 | |a Hepatic stellate cells induce gut tropism of CD8+ T lymphocytes | |
| 264 | 1 | |c 2015 | |
| 300 | |a XXII, 176 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |a Berlin, Techn. Univ., Diss., 2015 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028437174&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-028437174 | ||
Datensatz im Suchindex
| _version_ | 1804175357743464448 |
|---|---|
| adam_text | TABLE OF CONTENTS
TABLE OF CONTENTS
ABBREVIATIONS VII
LIST OF FIGURES XIV
LIST OF TABLES XVI
SUMMARY XIX
ZUSAMMENFASSUNG XXI
1 INTRODUCTION 1
1.1 THE INNATE AND THE ADAPTIVE IMMUNE SYSTEM 2
1.2 ANTIGEN PRESENTATION TO T LYMPHOCYTES 5
1.2.1 ACTIVATION OF T LYMPHOCYTES BY ANTIGEN-PRESENTING CELLS 5
1.2.2 ANTIGEN PRESENTATION TO T CELLS BY MAJOR HISTOCOMPATIBILITY
COMPLEX MOLECULES. 7
1.2.2.1 PEPTIDE PRESENTATION BY MHC CLASS I 7
1.2.2.2 PEPTIDE PRESENTATION BY MHC CLASS II 9
1.2.2.3 CROSS-PRESENTATION OF EXOGENOUS ANTIGENS BY MHC CLASS I 11
1.3 TISSUE MIGRATION OF T LYMPHOCYTES 14
1.3.1 HOMING OF NAIVE T CELLS TO SECONDARY LYMPHOID ORGANS 17
1.3.2 T CELL INSTRUCTION AND HOMING TO PERIPHERAL NON-LYMPHOID TISSUES
18
1.4 THE ANATOMY AND BIOLOGY OF THE LIVER 21
I
HTTP://D-NB.INFO/1081295511
TABLE OF CONTENTS
L.S NON-IMMUNOLOGICAL AND IMMUNOLOGICAL FUNCTIONS OF HEPATIC STELLATE
CELLS 24
2 AIMS OF THIS STUDY 29
3 MATERIALS 31
3.1 CELL CULTURE MEDIA 31
3.2 MICE 31
3.3 ANTIBODIES 32
3.4 PRIMERS USED FOR PCR 33
3.5 REAGENTS, CHEMICALS, AND CELL LINES 36
3.6 KITS 39
3.7 EQUIPMENT 39
3.8 SOFTWARE 42
3.9 BUFFERS 42
4 METHODS 49
4.1 ISOLATION OF HEPATIC STELLATE CELLS FROM MOUSE LIVERS 49
4.2 GENERATION OF BONE MARROW-DERIVED DENDRITIC CELLS 51
4.3 ISOLATION OF T LYMPHOCYTES FROM SPLEENS AND MESENTERIC LYMPH NODES
51
4.4 ISOLATION OF T LYMPHOCYTES FROM PEYER S PATCHES AND THE SMALL
INTESTINAL MUCOSA 52
4.5 T CELL INSTRUCTION ASSAYS 54
4.6 KILLING ASSAYS OF INSTRUCTED CD8* T LYMPHOCYTES 55
II
TABLE OF CONTENTS
4.7 TRANSWELL CHEMOTAXIS ASSAYS 56
4.8 COMPETITIVE ADOPTIVE T CELL TRANSFERS 56
4.9 GUT HOMING EXPERIMENTS 57
4.10 ISOLATION OF LIVER SINUSOIDAL ENDOTHELIAL CELLS AND KUPFFER CELLS
FROM MURINE LIVERS. 57
4.11 MAGNETIC-ACTIVATED CELL SORTING OF CELLS 58
4.12 FLOW CYTOMETRY 59
4.12.1 FACS ANALYSIS 60
4.12.2 FACS SORTING 60
4.13 RNA ISOLATION FROM CULTURED CELLS AND TISSUES 61
4.14 REVERSE TRANSCRIPTION OF RNA AND REAL-TIME POLYMERASE CHAIN
REACTIONS 61
4.15 CONVENTIONAL PCR FOR DETECTION OF RETINOL-CONVERTING ENZYMES 63
4.16 GENOTYPINGOF MICE 64
4.17 PHENOTYPING OF CI-4 TRANSGENIC MICE 70
4.18 IMMUNOFLUORESCENCE MICROSCOPY 70
4.18.1 HISTOLOGY AND IMMUNOFLUORESCENCE MICROSCOPY OF ORGAN SECTIONS 70
4.18.2 IMMUNOFLUORESCENCE MICROSCOPY OF CULTURED STELLATE CELLS 72
4.19 REVERSED-PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY 72
4.20 MOUSE LIVER TRANSPLANTATIONS 73
III
TABLE OF CONTENTS
4.21 MICROARRAYS OF LIVER-RESIDENT CELLS AND SCREENINGS FOR
TRANSCRIPTIONAL HSC SIGNATURES
74
4.22 GENERATION OF BMPLO-ICREERT2 AND BCOL-IDTR MICE 75
4.23 STATISTICAL ANALYSIS 77
5 RESULTS 78
5.1 HEPATIC STELLATE CELLS CAN CONVERT RETINOL TO RETINOIC ACID FOR
SUBSEQUENT SECRETION
78
5.2 HEPATIC STELLATE CELLS INDUCE THE EXPRESSION OF GUT HOMING RECEPTORS
IN CD8* T CELLS
IN VITRO 81
5.3 HSC-INSTRUCTED T LYMPHOCYTES PROLIFERATE AND ACQUIRE A
PRO-INFLAMMATORY
PHENOTYPE 83
5.4 ISOLATION OF HSCS YIELDS PURE POPULATIONS OF QUIESCENT HEPATIC
STELLATE CELLS 86
5.5 STELLATE CELL-INSTRUCTED GUT TROPISM OF T LYMPHOCYTES DEPENDS ON
RETINOIC ACID .... 89
5.6 HSC-INSTRUCTED T LYMPHOCYTES RESPOND TO CCL25 AND MIGRATE TO THE
INTESTINE 92
5.7 ANTIGEN-SPECIFIC CD8* T LYMPHOCYTES FAIL TO MIGRATE TO THE SMALL
INTESTINE FOLLOWING
DEPLETION OF GFAP* CELLS IN VIVO 95
5.8 T CELL HOMING TO THE INTESTINE IS INHIBITED FOLLOWING DEPLETION OF
GFAP* CELLS IN A
MURINE MODEL OF ORTHOTOPIC LIVER TRANSPLANTATION 99
5.9 GENERATION OF A SPECIFIC AND EFFICIENT STELLATE CELL DEPLETION MODEL
101
5.9.1 IDENTIFICATION OF NEW GENETIC MARKERS FOR QUIESCENT HEPATIC
STELLATE CELLS 102
5.9.2 STELLATE CELLS SPECIFICALLY EXPRESS BMPLO AMONG LIVER-RESIDENT
CELLS 104
IV
TABLE OF CONTENTS
5.9.3 THE CONCOMITANT EXPRESSION OF BMPLO AND BCOL IS A UNIQUE
CHARACTERISTIC OF
HEPATIC STELLATE CELLS 105
5.9.4 IMMUNOFLUORESCENCE MICROSCOPY CONFIRMS BMP10 PROTEIN EXPRESSION BY
STELLATE
CELLS IN VITRO AND IN VIVO 108
5.9.5 PROPOSED MODEL FOR THE DEPLETION OF QUIESCENT HEPATIC STELLATE
CELLS BASED ON
THE SIMULTANEOUS EXPRESSION OF BMPLO AND BCOL 110
5.9.6 STELLATE CELLS SPECIFICALLY EXPRESS TOMATO RED AFTER TAMOXIFEN
TREATMENT OF
BMPJ0-ICREERT2 X FLOSO26-TDTOMATO REPORTER MICE 112
6 DISCUSSION 115
6.1 HSCS SYNTHESIZE AND SECRETE RA FROM THEIR STORED POOLS OF RETINOL
116
6.2 HSCS CROSS-PRESENT ANTIGENS AND INDUCE DIFFERENTIATION OF NAIVE CD8*
T CELLS TO PRO
INFLAMMATORY EFFECTOR T CELLS 119
6.3 STELLATE CELLS INDUCE GUT TROPISM OF CD8* T LYMPHOCYTES BY SECRETION
OF RA 122
6.4 T CELLS INSTRUCTED BY HSCS ARE ABLE TO RESPOND TO CCL25 AND HOME TO
THE INTESTINE
125
6.5 GUT HOMING OF T LYMPHOCYTES IS REDUCED IN GFAP-CRE X KL IDTR TG MICE
FOLLOWING DT
TREATMENT 126
6.6 A NEW IN VIVO MODEL OF STELLATE CELL DEPLETION BASED ON THE
CONCOMITANT EXPRESSION
OF BMPLO AND BCOL BY HEPATIC STELLATE CELLS 130
7 REFERENCES 136
APPENDIX 160
V
TABLE OF CONTENTS
A. MICROARRAY DATA OF SELECTED GENES FROM LIVER-RESIDENT CELLS AND CELLS
FROM THE
IMMGEN DATABASE 160
B. PUBLICATIONS 170
C. ORAL PRESENTATIONS 171
D. POSTER PRESENTATIONS 172
E. AWARDS AND SCHOLARSHIPS 172
F. CURRICULUM VITAE 173
G. EXECUTION AND FINANCIAL SUPPORT OF THIS THESIS 174
ACKNOWLEDGEMENTS 175
EIDESSTATTLLCHE ERKLARUNG 176
VI
|
| any_adam_object | 1 |
| author | Maschmeyer, Patrick |
| author_GND | (DE-588)107892547X |
| author_facet | Maschmeyer, Patrick |
| author_role | aut |
| author_sort | Maschmeyer, Patrick |
| author_variant | p m pm |
| building | Verbundindex |
| bvnumber | BV043012252 |
| ctrlnum | (OCoLC)935114448 (DE-599)BVBBV043012252 |
| format | Thesis Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01163nam a2200289 c 4500</leader><controlfield tag="001">BV043012252</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">00000000000000.0</controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">151117s2015 ad|| m||| 00||| eng d</controlfield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)935114448</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BVBBV043012252</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-83</subfield><subfield code="a">DE-91</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Maschmeyer, Patrick</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)107892547X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes</subfield><subfield code="c">vorgelegt von Patrick Maschmeyer</subfield></datafield><datafield tag="246" ind1="1" ind2=" "><subfield code="a">Hepatic stellate cells induce gut tropism of CD8+ T lymphocytes</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">XXII, 176 S.</subfield><subfield code="b">Ill., graph. Darst.</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="502" ind1=" " ind2=" "><subfield code="a">Berlin, Techn. Univ., Diss., 2015</subfield></datafield><datafield tag="655" ind1=" " ind2="7"><subfield code="0">(DE-588)4113937-9</subfield><subfield code="a">Hochschulschrift</subfield><subfield code="2">gnd-content</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">DNB Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028437174&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-028437174</subfield></datafield></record></collection> |
| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV043012252 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T07:15:00Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-028437174 |
| oclc_num | 935114448 |
| open_access_boolean | |
| owner | DE-83 DE-91 DE-BY-TUM |
| owner_facet | DE-83 DE-91 DE-BY-TUM |
| physical | XXII, 176 S. Ill., graph. Darst. |
| publishDate | 2015 |
| publishDateSearch | 2015 |
| publishDateSort | 2015 |
| record_format | marc |
| spelling | Maschmeyer, Patrick Verfasser (DE-588)107892547X aut Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes vorgelegt von Patrick Maschmeyer Hepatic stellate cells induce gut tropism of CD8+ T lymphocytes 2015 XXII, 176 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Berlin, Techn. Univ., Diss., 2015 (DE-588)4113937-9 Hochschulschrift gnd-content DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028437174&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Maschmeyer, Patrick Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes |
| subject_GND | (DE-588)4113937-9 |
| title | Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes |
| title_alt | Hepatic stellate cells induce gut tropism of CD8+ T lymphocytes |
| title_auth | Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes |
| title_exact_search | Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes |
| title_full | Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes vorgelegt von Patrick Maschmeyer |
| title_fullStr | Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes vorgelegt von Patrick Maschmeyer |
| title_full_unstemmed | Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes vorgelegt von Patrick Maschmeyer |
| title_short | Hepatic stellate cells induce gut tropism of CD8 + T lymphocytes |
| title_sort | hepatic stellate cells induce gut tropism of cd8 t lymphocytes |
| topic_facet | Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028437174&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT maschmeyerpatrick hepaticstellatecellsinduceguttropismofcd8tlymphocytes |