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Caspase-8 in T-lymphocytes: An effec...

Salmena, Leonardo.

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Caspase-8 in T-lymphocytes: An effector of apoptosis and modulator of activation-induced proliferation and T-cell immunity.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Caspase-8 in T-lymphocytes: An effector of apoptosis and modulator of activation-induced proliferation and T-cell immunity./
作者:	Salmena, Leonardo.
面頁冊數:	171 p.
附註:	Source: Dissertation Abstracts International, Volume: 66-10, Section: B, page: 5312.
Contained By:	Dissertation Abstracts International66-10B.
標題:	Health Sciences, Immunology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR07740
ISBN:	9780494077405

Caspase-8 in T-lymphocytes: An effector of apoptosis and modulator of activation-induced proliferation and T-cell immunity.
Salmena, Leonardo.

Caspase-8 in T-lymphocytes: An effector of apoptosis and modulator of activation-induced proliferation and T-cell immunity. - 171 p.

Source: Dissertation Abstracts International, Volume: 66-10, Section: B, page: 5312.

Thesis (Ph.D.)--University of Toronto (Canada), 2005.

Caspase-8, an aspartate-specific cysteine protease, is best known for its ability to activate cell death via death receptors such as CD95 (Fas/Apo1). Recent evidence indicates that caspase-8 also has non-apoptotic functions in the transduction of signals via T-cell, B-cell and Toll-like receptors on lymphocytes. Previously, the in vivo role of caspase-8 has eluded analysis in post-natal tissues due to embryonic lethality associated with its deletion in mice. To circumvent embryonic lethality we generated mice with targeted caspase 8 disruption that is restricted to T-lymphocytes (tcasp8 -/-). Caspase-8 ablation protected T-lymphocytes from CD95 ligand but not anti-CD3 induced apoptosis, or apoptosis activated with agents that are known to act through the mitochondria. Importantly, these mice manifested a decrease in the number of peripheral T-cells and impaired activation induced T-cell proliferation (AITP). Caspase 8 mutant mice were unable to mount an immune response to viral infection, indicating that caspase 8 deletion in T-cells leads to immunodeficiency. Furthermore, mice lacking caspase-8 in T-cells developed a lethal, age dependent lymphoproliferative and lymphoinfiltrative immune disorder. With age, tcasp8 -/- mice developed lymphoadenopathy, splenomegaly and accumulated non-clonal T-cell infiltrates in lung, liver and kidneys accompanied by tissue damage. Casp8-/- T-cells isolated from old mice were in a perpetual state of activation in the absence of any infection or stimulation, which could account for the observed pathological phenotypes. These findings identify an essential, cell stage-specific role for caspase 8 in T-cell homeostasis and T-cell mediated immunity. Also, these studies uncover novel physiological functions for caspase-8 in immune regulation and function.

ISBN: 9780494077405Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Caspase-8 in T-lymphocytes: An effector of apoptosis and modulator of activation-induced proliferation and T-cell immunity.
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