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

  • Author / Creator
    Kelly, Stephanie Alicia Wilhelmina
  • 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
  • Graduation date
    Spring 2014
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • 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.