Separation from self explains failure of circulating T-cells to respond to the CD28 superagonist TGN1412:
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| Main Author: | |
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| Format: | Thesis Book |
| Language: | English |
| Published: |
2012
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| Subjects: | |
| Online Access: | Volltext Inhaltsverzeichnis |
| Item Description: | Online erschienen: 2013. - Zsfassung in dt. und engl. Sprache |
| Physical Description: | IX, 110 Bl. Ill., graph. Darst. |
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| 100 | 1 | |a Romer Roche, Paula Sofia |d 1983- |e Verfasser |0 (DE-588)1044442247 |4 aut | |
| 245 | 1 | 0 | |a Separation from self explains failure of circulating T-cells to respond to the CD28 superagonist TGN1412 |c von Paula Sofia Romer Roche |
| 246 | 1 | 3 | |a Verlust der "Selbst"-Erkennung erklärt die fehlende Reaktion zirkulierender T-Zellen auf den CD28-Superagonisten TGN1412 |
| 264 | 1 | |c 2012 | |
| 300 | |a IX, 110 Bl. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Online erschienen: 2013. - Zsfassung in dt. und engl. Sprache | ||
| 502 | |a Würzburg, Univ., Diss., 2012 | ||
| 650 | 0 | 7 | |a T-Lymphozyten-Rezeptor |0 (DE-588)4265934-6 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Monoklonaler Antikörper |0 (DE-588)4040094-3 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Antigen CD28 |0 (DE-588)4404583-9 |2 gnd |9 rswk-swf |
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| 912 | |a ebook | ||
| 943 | 1 | |a oai:aleph.bib-bvb.de:BVB01-026883632 | |
Record in the Search Index
| _version_ | 1811184396796952576 |
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| adam_text |
VI
TABLE OF CONTENTS
SUMMARY 10
ZUSAMMENFASSUNG 11
1. INTRODUCTION 13
1.1. IMMUNE SYSTEM 13
1.1.1. T CELLS 14
1.1.1.1. STRUCTURE OF THE T CELL RECEPTOR AND T CELL RECEPTOR COMPLEX 14
1.1.1.2. T CELL ACTIVATION AND COSTIMULATION 14
1.1.1.2.A. T CELL RECEPTOR SIGNALING 15
1.1.1.2.B. CD28 COSTIMULATION 15
1.2. IMMUNE PATHOLOGIES 16
1.2.1. CLASSIC THERAPIES TO CONTROL AUTOIMMUNE DISEASES 17
1.2.2. BIOLOGIES 17
1.3. IMMUNOMODULATORY MONOCLONAL ANTIBODIES 18
1.3.1. MURONOMAB (ORTHOCLONE OKT3) 18
1.4. REGULATORY T CELLS AS A TARGET FOR THERAPY 18
1.4.1. CONVENTIONAL AND SUPERAGONISTIC ANTI-CD28 MABS 19
1.4.1.1. SIGNALING PATHWAYS OF CD28 SUPERAGONISTIC MABS 20
1.4.2. IN VITRO REGULATORY T CELL EXPANSION BY ACD28 CONVENTIONAL AND
SUPERAGONISTIC MABS 21
1.5. CD28SA PRECLINICAL RODENT MODELS 22
1.5.1. STUDIES IN MICE AND RATS 22
1.5.2. CD28SA IN AUTOIMMUNE AND INFLAMMATORY DISEASE MODELS 23
1.6. TGN1412-A HUMAN ANTI-CD28 SUPERAGONISTIC MONOCLONAL ANTIBODY 25
1.6.1. TGN1412 PRECLINICAL STUDIES - ANIMAL MODELS 25
HTTP://D-NB.INFO/1044803150
VII
1.6.2. TGN1412 FIRST-IN-MAN CLINICAL TRIAL 25
1.6.3. CURRENT KNOWLEDGE ON CD28 SUPERAGONISTS - AFTER THE CRS 26
2. INTRODUCTORY STATEMENT ON CONTRIBUTIONS AND PREVIOUS PUBLICATION 27
3. METHODS 28
3.1. CELL ISOLATION AND PREPARATION 28
3.1.1. HUMAN PBMC ISOLATION 28
3.1.2. HUMAN LYMPH NODE CELLS 28
3.1.3. CELL CULTURE 28
3.1.4. FREEZING AND THAWING 28
3.1.5. DEPLETION AND ISOLATION OF CELL SUBSETS 29
3.2. STIMULATION ASSAYS - RESTORE PROTOCOL 29
3.3. WESTERN BLOTTING 29
3.3.1. CELL LYSIS 29
3.3.2. PRE-CLEARING OF CELL LYSATE 30
3.3.3. SDS-POLYACRYLAMIDE GEL ELECTROPHORESIS 30
3.3.4. WESTERN BLOT 30
3.4. CELL PROLIFERATION ASSAYS 30
3.4.1. 3H-THYMIDINE INCORPORATION 30
3.4.2. KI67 STAINING 30
3.5. CELL DISSOCIATION EXPERIMENT 31
3.6. TRANSWELL ASSAY 31
3.7. FLOW CYTOMETRY (PHENOTYPING) 31
3.8. CYTOKINE RELEASE QUANTIFICATION 31
3.8.1. INTRACELLULAR CYTOKINE STAINING 32
3.8.2. RESPONDING CELL SUBSET DETERMINATION 32
3.9. CFSE LABELING 32
VIII
3.10. CONFOCAL MICROSCOPY 32
3.11. STATISTICAL ANALYSIS 33
4. RESULTS 34
4.1. PBMC RESPONSE TO SOLUBLE TGN1412 34
4.2. OPTIMIZATION OF THE RESTORE PROTOCOL 36
4.3. LOSS OF SUPPRESSION VS. GAIN OF FUNCTION AFTER HIGH-DENSITY
PRECULTURE 37
4.4. PROPERTIES OF THE RESTORE RESPONSE OF PBMC TO SOLUBLE TGN1412 39
4.5. CELLULAR INTERACTIONS DURING HIGH-DENSITY PRECULTURE 41
4.6. HUMAN LYMPH NODE T CELL RESPONSE TO TGN1412 52
4.1. PHARMACOLOGIC INHIBITION OF THE PRECULTURED-T-CELLS RESPONSE 53
4.2. RESPONSE TO T-CELL MITOGENS 56
4.3. RESPONSE OF PRECULTURED PBMC TO BACTERIAL ANTIGENS 58
4.4. ROLE OF THE FC PORTION OF CD28 SUPERAGONISTS ON T- CELL STIMULATION
59
5. DISCUSSION 69
LIST OF FIGURES 80
ANNEX 83
MATERIALS 83
CHEMICALS AND REAGENTS 83
ENZYMES AND INHIBITORS 84
COMMERCIAL KITS 84
MAGNETIC BEADS FOR CELL ISOLATION OR DEPLETION 84
RADIOACTIVE MATERIALS 84
ANTIBODIES AND SECONDARY REAGENTS 85
CELL STIMULATION-RELATED REAGENTS 87
BUFFERS, MEDIA AND SOLUTIONS 88
HUMAN CELLS 90
IX
EQUIPMENT AND SUPPLIES 90
SOFTWARE 91
LIST OF ABBREVIATIONS
AND ACRONYMS 93
REFERENCES 96
PUBLICATIONS 107
CURRICULUM VITAE 108 |
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| spelling | Romer Roche, Paula Sofia 1983- Verfasser (DE-588)1044442247 aut Separation from self explains failure of circulating T-cells to respond to the CD28 superagonist TGN1412 von Paula Sofia Romer Roche Verlust der "Selbst"-Erkennung erklärt die fehlende Reaktion zirkulierender T-Zellen auf den CD28-Superagonisten TGN1412 2012 IX, 110 Bl. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Online erschienen: 2013. - Zsfassung in dt. und engl. Sprache Würzburg, Univ., Diss., 2012 T-Lymphozyten-Rezeptor (DE-588)4265934-6 gnd rswk-swf Monoklonaler Antikörper (DE-588)4040094-3 gnd rswk-swf Antigen CD28 (DE-588)4404583-9 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Antigen CD28 (DE-588)4404583-9 s T-Lymphozyten-Rezeptor (DE-588)4265934-6 s Monoklonaler Antikörper (DE-588)4040094-3 s DE-604 Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:20-opus-74933 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-74933 Resolving-System kostenfrei Volltext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026883632&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Romer Roche, Paula Sofia 1983- Separation from self explains failure of circulating T-cells to respond to the CD28 superagonist TGN1412 T-Lymphozyten-Rezeptor (DE-588)4265934-6 gnd Monoklonaler Antikörper (DE-588)4040094-3 gnd Antigen CD28 (DE-588)4404583-9 gnd |
| subject_GND | (DE-588)4265934-6 (DE-588)4040094-3 (DE-588)4404583-9 (DE-588)4113937-9 |
| title | Separation from self explains failure of circulating T-cells to respond to the CD28 superagonist TGN1412 |
| title_alt | Verlust der "Selbst"-Erkennung erklärt die fehlende Reaktion zirkulierender T-Zellen auf den CD28-Superagonisten TGN1412 |
| title_auth | Separation from self explains failure of circulating T-cells to respond to the CD28 superagonist TGN1412 |
| title_exact_search | Separation from self explains failure of circulating T-cells to respond to the CD28 superagonist TGN1412 |
| title_full | Separation from self explains failure of circulating T-cells to respond to the CD28 superagonist TGN1412 von Paula Sofia Romer Roche |
| title_fullStr | Separation from self explains failure of circulating T-cells to respond to the CD28 superagonist TGN1412 von Paula Sofia Romer Roche |
| title_full_unstemmed | Separation from self explains failure of circulating T-cells to respond to the CD28 superagonist TGN1412 von Paula Sofia Romer Roche |
| title_short | Separation from self explains failure of circulating T-cells to respond to the CD28 superagonist TGN1412 |
| title_sort | separation from self explains failure of circulating t cells to respond to the cd28 superagonist tgn1412 |
| topic | T-Lymphozyten-Rezeptor (DE-588)4265934-6 gnd Monoklonaler Antikörper (DE-588)4040094-3 gnd Antigen CD28 (DE-588)4404583-9 gnd |
| topic_facet | T-Lymphozyten-Rezeptor Monoklonaler Antikörper Antigen CD28 Hochschulschrift |
| url | https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-74933 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026883632&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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