ERA

Download the full-sized PDF of Regulation of FasL expression and trafficking in cytotoxic T lymphocytesDownload the full-sized PDF

Analytics

Share

Permanent link (DOI): https://doi.org/10.7939/R3WH03

Download

Export to: EndNote  |  Zotero  |  Mendeley

Communities

This file is in the following communities:

Graduate Studies and Research, Faculty of

Collections

This file is in the following collections:

Theses and Dissertations

Regulation of FasL expression and trafficking in cytotoxic T lymphocytes Open Access

Descriptions

Other title
Subject/Keyword
cytotoxicity
T cells
Fas ligand
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
He, Jinshu
Supervisor and department
Ostergaard, Hanne (Medical Microbiology and Immunology)
Examining committee member and department
Watts, Tania (Immunology, University of Toronto)
Barry, Michele (Medical Microbiology and Immunology)
Bleackley, R. Chris (Biochemistry)
Lacy, Paige (Medicine)
Department
Department of Medical Microbiology and Immunology
Specialization

Date accepted
2009-08-28T15:26:55Z
Graduation date
2009-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Cytotoxic T lymphocytes (CTL) are differentiated CD8+ T cells that eliminate virally infected cells and tumor cells. CTL lyse target cells by at least two distinct mechanisms: degranulation of cytolytic molecules and cell surface expression of Fas ligand (FasL), which induces apoptosis of Fas-expressing target cells. In addition to their defense function, these two cytolytic mechanisms also play crucial roles in homeostatic regulation and contribute to pathogenesis in many different model systems. To fully exploit killer cells in tumor and virus elimination, or dampen the immune response in, for example, autoimmune diseases, it is essential to understand the mechanisms that CTL employ to destroy target cells. In contrast to the well-characterized degranulation mechanism, the regulation of FasL expression on the CTL cell surface remains elusive and even controversial. The prevailing model at the time I initiated my studies was that FasL is stored in cytolytic granules and that FasL cell surface expression would be subject to the same controls as degranulation. In this thesis, I revealed for the first time that there are two waves of FasL cell surface expression upon target cell engagement, which are differentially regulated by TCR signaling and perform distinct roles in CTL mediated responses. I demonstrated that CTL degranulation and FasL lytic mechanisms are fully independent with respect to stored component localization and regulation. Finally, based on cell fractionation and imaging studies, I suggested that FasL is stored in a recycling endosome associated compartment, which is located in a special niche between the ER and mitochondria and uses a novel microtubule-independent secretory mechanism to translocate to the cell surface. Together, these findings provide important insight into the regulation and role of FasL in CTL mediated responses.
Language
English
DOI
doi:10.7939/R3WH03
Rights
License granted by Jinshu He (jinshu@ualberta.ca) on 2009-08-28T01:55:53Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication

File Details

Date Uploaded
Date Modified
2014-04-29T16:50:29.842+00:00
Audit Status
Audits have not yet been run on this file.
Characterization
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 22299080
Last modified: 2015:10:12 10:43:36-06:00
Filename: He_Jinshu_Fall 2009.pdf
Original checksum: 00dd7452a29d582d126b6597a1edfa91
Well formed: false
Valid: false
Status message: Invalid object number or object stream offset=1959
File title: Microsoft Word - He_Jinshu_Fall 2009_2.doc
File author: jinshu
Activity of users you follow
User Activity Date