iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Bonn
2020
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | VIII, 115 Seiten Illustrationen, Diagramme 30 cm |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV047213775 | ||
| 003 | DE-604 | ||
| 005 | 20210614 | ||
| 007 | t | ||
| 008 | 210325s2020 gw a||| m||| 00||| eng d | ||
| 015 | |a 21,H03 |2 dnb | ||
| 016 | 7 | |a 1223485994 |2 DE-101 | |
| 020 | |c Broschur | ||
| 035 | |a (OCoLC)1240339554 | ||
| 035 | |a (DE-599)DNB1223485994 | ||
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| 044 | |a gw |c XA-DE | ||
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| 100 | 1 | |a Heuser, Christoph |e Verfasser |0 (DE-588)1222930013 |4 aut | |
| 245 | 1 | 0 | |a iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming |c vorgelegt von Christoph Heuser |
| 264 | 1 | |a Bonn |c 2020 | |
| 300 | |a VIII, 115 Seiten |b Illustrationen, Diagramme |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Rheinische Friedrich-Wilhelms-Universität Bonn |d 2020 | ||
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| 999 | |a oai:aleph.bib-bvb.de:BVB01-032618528 | ||
Datensatz im Suchindex
| _version_ | 1804182330053492736 |
|---|---|
| adam_text | TABLE
OF
CONTENTS
INTRODUCTION
1
LAYERS
OF
THE
IMMUNE
SYSTEM
1
T
CELLS
ARE
PIVOTAL
PLAYERS
OF
THE
ADAPTIVE
IMMUNE
SYSTEM
1
THYMIC
SELECTION
OF
T
CELLS
2
FUNCTIONAL
DICHOTOMY
OF
CD4
+
AND
CD8
+
T
CELLS
2
SIGNALS
1-3
OF
T
CELL
PRIMING
3
DIFFERENTIATION
OF
EFFECTOR
AND
MEMORY
CD8
+
T
CELLS
4
T
CELL
PRIMING
OCCURS
IN
THREE
PHASES
6
NEGATIVE
REGULATORS
OF
CD8
T
CELL
RESPONSES
6
CD8
T
CELL
PRIMING
TO
EXOGENOUS
ANTIGENS
RELIES
ON
CROSS-PRESENTATION
7
T
CELL
HELP
FOR
CD8
T
CELL
PRIMING
7
CD40L
AS
MOLECULAR
EQUIVALENT
OF
HELP
7
EFFECTS
OF
T
CELL
HELP
ON
DCS
AND
CD8
T
CELLS
8
TEMPORAL
ASPECTS
OFT
CELL
HELP
9
SPATIAL
COORDINATION
OF
LICENSED
DCS
WITH
CD8
+
T
CELLS
10
CD4
T
CELL
HELP
BEYOND
PRIMING
10
NATURAL
KILLER
T
CELLS
ARE
A
LINEAGE
OF
UNCONVENTIONAL
T
CELLS
11
SUBSETS
OFNKT
CELLS
TOOLS
TO
STUDY
NKT
CELLS
IN
VIVO
AND
IN
SITU
13
RECOGNITION
OF
ENDOGENOUS
AND
EXOGENOUS
LIPIDS
14
INKT
CELLS
PROVIDE
TU-CELL
LIKE
HELP
14
PHYSIOLOGICAL
FUNCTIONS
OFNKT
CELLS
76
CLINICAL
APPLICATIONS
OFNKT
CELLS
17
AIMS
OF
THE
STUDY
18
MATERIALS
AND
METHODS
19
MATERIALS
19
TECHNICAL
EQUIPMENT.
19
CONSUMABLES
20
REAGENTS
H
FLOW
CYTOMETRY
ANTIBODIES
23
FLOW
CYTOMETRY
MULTIMERS
25
BLOCKING,
DEPLETING,
AND
STIMULATING
ANTIBODIES
25
BUFFERS
AND
MEDIA26
MOUSE
STRAINS
SOFTWARE
METHODS
.............................................................................................................................................................
30
MICE
&
TREATMENTS
VI
INKT
CELL
DEPLETION
BOOSTS
ALTERNATIVE
CROSS-PRIMING
CELLS
................................................................................................................................................................
31
FLOW
CYTOMETRY
...............................................................................................................................................
32
STATISTICAL
ANALYSIS
..........................................................................................................................................
35
RESULTS
..............................................................................................................................................................
37
XCR1
+
DENDRITIC
CELLS
ARE
ESSENTIAL
FOR
ALTERNATIVE
CROSS-PRIMING,
BUT
NOT
FOR
INKT
CELL
ACTIVATION
...............
37
CDCL
PROMOTE
THE
CD8
+
T
CELL
RESPONSE
LATE
DURING
CROSS-PRIMING
...................................................................
37
A
LACK
OF
TOOLS
HAMPERS
THE
VISUALIZATION
OFNKT
CELL
INTERACTIONS
..................................................................
39
INKT
CELLS
REDISTRIBUTE
TO
THE
SPLENIC
WHITE
PULP
AFTER
ACTIVATION
......................................................................
41
JAL8
-/
7THYL.L
MIXED
BONE
MARROW
CHIMERAS
ALLOW
FOR
THE
CONDITIONAL
DEPLETION
OF
INKT
CELLS
....................
41
THE
CIRCADIAN
TIME
OF
IMMUNIZATION
INFLUENCES
THE
PRIMARY
CD8
+
T
CELL
RESPONSE
.........................................
43
AG-SPECIFIC
CD8
+
T
CELLS
EXPAND
MORE
WHEN
INKT
CELLS
ARE
PRESENT
DURING
CTL
PRIMING
.............................
44
PLZF
1DTR
BONE
MARROW
CHIMERAS
ALLOW
FOR
THE
SPECIFIC
DEPLETION
OF
INKT
CELLS
............................................
46
NK
CELLS
DO
NOT
CRITICALLY
INFLUENCE
THE
CD8
+
T
CELL
RESPONSE
AFTER
ALTERNATIVE
CROSS-PRIMING
.........................
48
DEPLETION
OF
INKT
CELLS
20
HOURS
AFTER
IMMUNIZATION
BOOSTS
CD8
+
T
CELL
EXPANSION
AND
EFFECTOR
DIFFERENTIATION
....................................................................................................................................................
49
LATE
CD40L
SIGNALING
BOOSTS
CLASSICAL
AND
ALTERNATIVE
CROSS-PRIMING
.............................................................
52
MONOCYTIC
CELLS
UPREGULATE
SURFACE
CD40L
EXPRESSION
IN
AGC-IMMUNIZED
MICE
............................................
52
INKT
CELL
DEPLETION MINIMALLY
AFFECTS
DENDRITIC
CELL
FUNCTION
..........................................................................
55
STAT6
IS
PHOSPHORYLATED
TRANSIENTLY
IN
DCS
AND
T
CELLS
AFTER
INKT
CELL
ACTIVATION
........................................
56
STAT6
SIGNALING,
BUT
NOT
IL-4,
LIMITS
CD8
+
T
CELL
EXPANSION
.........................................................................
57
CXCR3
LIMITS
THE
EXPANSION
OF
AG-SPECIFIC
CD8
+
T
CELLS
INDEPENDENT
OF
IFNY
..............................................
59
PARADOXICAL
IMPAIRMENT
OF
THE
PRIMARY
CTL
RESPONSE
UPON
INKT
CELL
DEPLETION WHEN
STUDYING
MEMORY
FORMATION
............................................................................................................................................................
62
DEPLETION
OF
CONVENTIONAL
T
HELPER
CELLS
HAS
MINIMAL
EFFECTS
ON
THE
CD8
+
T
CELL
RESPONSE
.............................
63
DISCUSSION
........................................................................................................................................................
65
ESTABLISHMENT
OF
NOVEL
TOOLS
FOR
THE
CONDITIONAL
DEPLETION
OFNKT
CELLS
..........................................................
66
CD40L
+
NKT
CELLS
ACCUMULATE
IN
THE
WHITE
PULP
AFTER
ACTIVATION
...................................................................
68
NKT
CELL
DEPLETION
AND
CD40L
BLOCKADE
HAVE
OPPOSITE
EFFECTS
ON
THE
CD8
T
CELL
RESPONSE
...........................
69
NKT
CELL
DEPLETION
HAS
A
MIXED
EFFECT
ON
DC
FUNCTION
.....................................................................................
71
DEPLETION
OF
AG-SPECIFIC
T
H
CELLS
DOES
NOT
IMPACT
ON
THE
PRIMARY
CTL
RESPONSE
IN
CLASSICAL
CROSS-PRIMING..
71
SEQUENTIAL
INTERACTIONS
OFNKT
CELLS
AND
CD8
+
T
CELLS
WITH
DCS
ARE
SUFFICIENT
FOR
ALTERNATIVE
CROSS-PRIMING
73
PROTOTYPICAL
NKT
CELL
CYTOKINES
DO
NOT
MEDIATE
THE
DELAYED
NEGATIVE
FEEDBACK
..............................................
74
T
ABLE
OF
C
ONTENTS
VII
TWO
WAVES
OF
NKT-CELL
MEDIATED
SUPPRESSION
SAFEGUARD
THE
CD8
T
CELL
RESPONSE
........................................
76
DOES
T
CELL
HELP
INSULATE
MEMORY
PRECURSORS
FROM
INFLAMMATION?
..................................................................
78
NKT-CELL
HELP
IS
ALTERNATIVE
IN
MANY
WAYS
........................................................................................................
79
SORTING
THROUGH
THE
COMPONENTS
OF
T
CELL
HELP
IN
CROSS-PRIMING
.......................................................................
79
FUTURE
DIRECTIONS
................................................................................................................................................
81
ABBREVIATIONS
...............................................................................................................................................
83
REFERENCES
......................................................................................................................................................
87
PUBLICATIONS
................................................................................................................................................
113
ACKNOWLEDGEMENTS
...............................................................................................................................
115
|
| adam_txt |
TABLE
OF
CONTENTS
INTRODUCTION
1
LAYERS
OF
THE
IMMUNE
SYSTEM
1
T
CELLS
ARE
PIVOTAL
PLAYERS
OF
THE
ADAPTIVE
IMMUNE
SYSTEM
1
THYMIC
SELECTION
OF
T
CELLS
2
FUNCTIONAL
DICHOTOMY
OF
CD4
+
AND
CD8
+
T
CELLS
2
SIGNALS
1-3
OF
T
CELL
PRIMING
3
DIFFERENTIATION
OF
EFFECTOR
AND
MEMORY
CD8
+
T
CELLS
4
T
CELL
PRIMING
OCCURS
IN
THREE
PHASES
6
NEGATIVE
REGULATORS
OF
CD8
T
CELL
RESPONSES
6
CD8
T
CELL
PRIMING
TO
EXOGENOUS
ANTIGENS
RELIES
ON
CROSS-PRESENTATION
7
T
CELL
HELP
FOR
CD8
T
CELL
PRIMING
7
CD40L
AS
MOLECULAR
EQUIVALENT
OF
HELP
7
EFFECTS
OF
T
CELL
HELP
ON
DCS
AND
CD8
T
CELLS
8
TEMPORAL
ASPECTS
OFT
CELL
HELP
9
SPATIAL
COORDINATION
OF
LICENSED
DCS
WITH
CD8
+
T
CELLS
10
CD4
T
CELL
HELP
BEYOND
PRIMING
10
NATURAL
KILLER
T
CELLS
ARE
A
LINEAGE
OF
UNCONVENTIONAL
T
CELLS
11
SUBSETS
OFNKT
CELLS
TOOLS
TO
STUDY
NKT
CELLS
IN
VIVO
AND
IN
SITU
13
RECOGNITION
OF
ENDOGENOUS
AND
EXOGENOUS
LIPIDS
14
INKT
CELLS
PROVIDE
TU-CELL
LIKE
HELP
14
PHYSIOLOGICAL
FUNCTIONS
OFNKT
CELLS
76
CLINICAL
APPLICATIONS
OFNKT
CELLS
17
AIMS
OF
THE
STUDY
18
MATERIALS
AND
METHODS
19
MATERIALS
19
TECHNICAL
EQUIPMENT.
19
CONSUMABLES
20
REAGENTS
H
FLOW
CYTOMETRY
ANTIBODIES
23
FLOW
CYTOMETRY
MULTIMERS
25
BLOCKING,
DEPLETING,
AND
STIMULATING
ANTIBODIES
25
BUFFERS
AND
MEDIA26
MOUSE
STRAINS
SOFTWARE
METHODS
.
30
MICE
&
TREATMENTS
VI
INKT
CELL
DEPLETION
BOOSTS
ALTERNATIVE
CROSS-PRIMING
CELLS
.
31
FLOW
CYTOMETRY
.
32
STATISTICAL
ANALYSIS
.
35
RESULTS
.
37
XCR1
+
DENDRITIC
CELLS
ARE
ESSENTIAL
FOR
ALTERNATIVE
CROSS-PRIMING,
BUT
NOT
FOR
INKT
CELL
ACTIVATION
.
37
CDCL
PROMOTE
THE
CD8
+
T
CELL
RESPONSE
LATE
DURING
CROSS-PRIMING
.
37
A
LACK
OF
TOOLS
HAMPERS
THE
VISUALIZATION
OFNKT
CELL
INTERACTIONS
.
39
INKT
CELLS
REDISTRIBUTE
TO
THE
SPLENIC
WHITE
PULP
AFTER
ACTIVATION
.
41
JAL8
-/
7THYL.L
MIXED
BONE
MARROW
CHIMERAS
ALLOW
FOR
THE
CONDITIONAL
DEPLETION
OF
INKT
CELLS
.
41
THE
CIRCADIAN
TIME
OF
IMMUNIZATION
INFLUENCES
THE
PRIMARY
CD8
+
T
CELL
RESPONSE
.
43
AG-SPECIFIC
CD8
+
T
CELLS
EXPAND
MORE
WHEN
INKT
CELLS
ARE
PRESENT
DURING
CTL
PRIMING
.
44
PLZF
1DTR
BONE
MARROW
CHIMERAS
ALLOW
FOR
THE
SPECIFIC
DEPLETION
OF
INKT
CELLS
.
46
NK
CELLS
DO
NOT
CRITICALLY
INFLUENCE
THE
CD8
+
T
CELL
RESPONSE
AFTER
ALTERNATIVE
CROSS-PRIMING
.
48
DEPLETION
OF
INKT
CELLS
20
HOURS
AFTER
IMMUNIZATION
BOOSTS
CD8
+
T
CELL
EXPANSION
AND
EFFECTOR
DIFFERENTIATION
.
49
LATE
CD40L
SIGNALING
BOOSTS
CLASSICAL
AND
ALTERNATIVE
CROSS-PRIMING
.
52
MONOCYTIC
CELLS
UPREGULATE
SURFACE
CD40L
EXPRESSION
IN
AGC-IMMUNIZED
MICE
.
52
INKT
CELL
DEPLETION MINIMALLY
AFFECTS
DENDRITIC
CELL
FUNCTION
.
55
STAT6
IS
PHOSPHORYLATED
TRANSIENTLY
IN
DCS
AND
T
CELLS
AFTER
INKT
CELL
ACTIVATION
.
56
STAT6
SIGNALING,
BUT
NOT
IL-4,
LIMITS
CD8
+
T
CELL
EXPANSION
.
57
CXCR3
LIMITS
THE
EXPANSION
OF
AG-SPECIFIC
CD8
+
T
CELLS
INDEPENDENT
OF
IFNY
.
59
PARADOXICAL
IMPAIRMENT
OF
THE
PRIMARY
CTL
RESPONSE
UPON
INKT
CELL
DEPLETION WHEN
STUDYING
MEMORY
FORMATION
.
62
DEPLETION
OF
CONVENTIONAL
T
HELPER
CELLS
HAS
MINIMAL
EFFECTS
ON
THE
CD8
+
T
CELL
RESPONSE
.
63
DISCUSSION
.
65
ESTABLISHMENT
OF
NOVEL
TOOLS
FOR
THE
CONDITIONAL
DEPLETION
OFNKT
CELLS
.
66
CD40L
+
NKT
CELLS
ACCUMULATE
IN
THE
WHITE
PULP
AFTER
ACTIVATION
.
68
NKT
CELL
DEPLETION
AND
CD40L
BLOCKADE
HAVE
OPPOSITE
EFFECTS
ON
THE
CD8
T
CELL
RESPONSE
.
69
NKT
CELL
DEPLETION
HAS
A
MIXED
EFFECT
ON
DC
FUNCTION
.
71
DEPLETION
OF
AG-SPECIFIC
T
H
CELLS
DOES
NOT
IMPACT
ON
THE
PRIMARY
CTL
RESPONSE
IN
CLASSICAL
CROSS-PRIMING.
71
SEQUENTIAL
INTERACTIONS
OFNKT
CELLS
AND
CD8
+
T
CELLS
WITH
DCS
ARE
SUFFICIENT
FOR
ALTERNATIVE
CROSS-PRIMING
73
PROTOTYPICAL
NKT
CELL
CYTOKINES
DO
NOT
MEDIATE
THE
DELAYED
NEGATIVE
FEEDBACK
.
74
T
ABLE
OF
C
ONTENTS
VII
TWO
WAVES
OF
NKT-CELL
MEDIATED
SUPPRESSION
SAFEGUARD
THE
CD8
T
CELL
RESPONSE
.
76
DOES
T
CELL
HELP
INSULATE
MEMORY
PRECURSORS
FROM
INFLAMMATION?
.
78
NKT-CELL
HELP
IS
ALTERNATIVE
IN
MANY
WAYS
.
79
SORTING
THROUGH
THE
COMPONENTS
OF
T
CELL
HELP
IN
CROSS-PRIMING
.
79
FUTURE
DIRECTIONS
.
81
ABBREVIATIONS
.
83
REFERENCES
.
87
PUBLICATIONS
.
113
ACKNOWLEDGEMENTS
.
115 |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| author | Heuser, Christoph |
| author_GND | (DE-588)1222930013 |
| author_facet | Heuser, Christoph |
| author_role | aut |
| author_sort | Heuser, Christoph |
| author_variant | c h ch |
| building | Verbundindex |
| bvnumber | BV047213775 |
| ctrlnum | (OCoLC)1240339554 (DE-599)DNB1223485994 |
| discipline | Medizin |
| discipline_str_mv | Medizin |
| format | Thesis Book |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV047213775 |
| illustrated | Illustrated |
| index_date | 2024-07-03T16:55:13Z |
| indexdate | 2024-07-10T09:05:50Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-032618528 |
| oclc_num | 1240339554 |
| open_access_boolean | |
| owner | DE-29T DE-355 DE-BY-UBR |
| owner_facet | DE-29T DE-355 DE-BY-UBR |
| physical | VIII, 115 Seiten Illustrationen, Diagramme 30 cm |
| publishDate | 2020 |
| publishDateSearch | 2020 |
| publishDateSort | 2020 |
| record_format | marc |
| spelling | Heuser, Christoph Verfasser (DE-588)1222930013 aut iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming vorgelegt von Christoph Heuser Bonn 2020 VIII, 115 Seiten Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Rheinische Friedrich-Wilhelms-Universität Bonn 2020 Natürliche Killerzelle (DE-588)4171290-0 gnd rswk-swf Signaltransduktion (DE-588)4318717-1 gnd rswk-swf Immunreaktion (DE-588)4133841-8 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Natürliche Killerzelle (DE-588)4171290-0 s Immunreaktion (DE-588)4133841-8 s Signaltransduktion (DE-588)4318717-1 s DE-604 B:DE-101 application/pdf https://d-nb.info/1223485994/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032618528&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Heuser, Christoph iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming Natürliche Killerzelle (DE-588)4171290-0 gnd Signaltransduktion (DE-588)4318717-1 gnd Immunreaktion (DE-588)4133841-8 gnd |
| subject_GND | (DE-588)4171290-0 (DE-588)4318717-1 (DE-588)4133841-8 (DE-588)4113937-9 |
| title | iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming |
| title_auth | iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming |
| title_exact_search | iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming |
| title_exact_search_txtP | iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming |
| title_full | iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming vorgelegt von Christoph Heuser |
| title_fullStr | iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming vorgelegt von Christoph Heuser |
| title_full_unstemmed | iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming vorgelegt von Christoph Heuser |
| title_short | iNKT cell depletion and STAT6 inhibition boost the expansion of cytotoxic T cells in alternative cross-priming |
| title_sort | inkt cell depletion and stat6 inhibition boost the expansion of cytotoxic t cells in alternative cross priming |
| topic | Natürliche Killerzelle (DE-588)4171290-0 gnd Signaltransduktion (DE-588)4318717-1 gnd Immunreaktion (DE-588)4133841-8 gnd |
| topic_facet | Natürliche Killerzelle Signaltransduktion Immunreaktion Hochschulschrift |
| url | https://d-nb.info/1223485994/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032618528&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT heuserchristoph inktcelldepletionandstat6inhibitionboosttheexpansionofcytotoxictcellsinalternativecrosspriming |
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