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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
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- Author / Creator
- Kelly, Stephanie Alicia Wilhelmina
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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. -
- Subjects / Keywords
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- Graduation date
- Spring 2014
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- Type of Item
- Thesis
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- Degree
- Master of Science
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- License
- This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.