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Permanent link (DOI): https://doi.org/10.7939/R3R49GJ1X

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Examining the origin of peripheral self-reactive T cells and the contribution of Gadd45beta to T cell selection events in the HYcd4 TCR transgenic mouse model Open Access

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Other title
Subject/Keyword
TCR transgenic mouse model
T cell negative selection
PD-1 and Gadd45beta
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Kelly, Stephanie Alicia Wilhelmina
Supervisor and department
Baldwin, Troy (Medical Microbiology and Immunology)
Examining committee member and department
Anderson, Colin (Surgery/Medical Microbiology and Immunology)
Cameron, Lisa (Medicine/Pulmonary Research Group)
Kane, Kevin (Medical Microbiology and Immunology)
Department
Department of Medical Microbiology and Immunology
Specialization
Immunology
Date accepted
2014-01-07T15:44:27Z
Graduation date
2014-06
Degree
Master of Science
Degree level
Master's
Abstract
Thymic negative selection is important for preventing self-reactive T cells from entering the circulation. However, some self-reactive T cell clones can escape negative selection and induce autoimmunity. The molecular pathways that regulate negative selection are currently unclear, but PD-1 and Gadd45β have been implicated. Using the HYcd4 mouse model, we found an absence of self-reactive CD8SP thymocytes, but the presence of self-reactive T cells in the periphery in adult mice. Ontogeny studies demonstrated the presence of self-specific DP and CD8+ T cells in the periphery at Day 3 post-birth that expressed the co-inhibitory receptor PD-1. The presence of self-reactive T cells was not dependent on negative selection occurring in a neonatal thymus. By studying Gadd45β deficient mice, no evidence was found to support a role for Gadd45β in negative selection. Collectively, these data shed light on the source of self-reactive peripheral T cells and the molecular mechanism underlying negative selection.
Language
English
DOI
doi:10.7939/R3R49GJ1X
Rights
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 these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before 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.
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File title: Kelly_Stephanie_Spring 2014
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