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| Identifier |
000383019 |
| Title |
Programmed-death receptor (PD-1) and its role in T cell biology |
| Alternative Title |
Μελέτη του ρόλου του PD-1 στην βιολογία των Τ-λεμφοκυττάρων |
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Author
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Charlton, Joanna
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Thesis advisor
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Μαυροθαλασσίτης , Γεώργιος
Μαμαλάκη, Κλειώ
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| Abstract |
Memory-phenotype (MP) T cells, found in unimmunized mice, display phenotypic and
functional traits of memory cells and provide essential protection against infections, playing a
role in both innate and adaptive immune responses. Mechanisms governing homeostasis of
these MP T cells remain ill defined. In this paper, we reveal a crucial role of the negative costimulator
Programmed Death-1 (PD-1) in regulating developmental fates of memoryphenotype
cells. Thus, in lymphoid organs and tissues of PD-1 KO mice a marked
accumulation of functional effector memory-(TEM) phenotype CD8 T cells was observed. TEMphenotype
cells from PD-1 KO mice exhibit decreased proliferation but increased survival
potential. These cells could produce effector molecules constitutively, in response to
phorbol esters or through bystander activation by innate stimuli. Similarly, in lymphopeniainduced
proliferating (LIP) CD8 T cells, whereby normally naïve T cells acquire a memoryphenotype,
skewing towards a TEM phenotype was prominent in the absence of PD-1.
Acquisition of the TEM-phenotype was a CD8 T cell-intrinsic phenomenon as demonstrated
by mixed bone marrow transfer experiments. Importantly, adoptively transferred PD-1 KO
CD8 central memory (TCM) cells converted into the TEM-phenotype indicating that PD-1 sets a
major checkpoint in the TCM →TEM-phenotype differentiation process. This was reflected by
distinct patterns of gene expression of PD-1 KO TCM-phenotype cells revealed by global
transcriptional analysis. Additionally, adoptively transferred PD-1 KO TEM-phenotype cells
converted to a lesser degree to a TCM-phenotype. Together, these data suggest that PD-1
shapes memory-phenotype CD8 T cell subsets.
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| Language |
English |
| Subject |
Central memory T cells (TCM) |
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Effector memory T cells (TEM) |
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Homeostasis |
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Memory phenotype (MP) cells |
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Programmed death receptor (PD-1) |
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Αρνητικός συνενεργοποιητής |
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Κύτταρα δραστικής μνήμης |
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Κύτταρα κεντρικής μνήμης |
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Ομοιόσταση |
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Φαινότυπο κυττάρων μνήμης |
| Issue date |
2014-01-22 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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| Views |
268 |
Programmed-death receptor (PD-1) and its role in T cell biology
