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

  • TCR transgenic mouse model
  • PD-1 and Gadd45beta
  • T cell negative selection

• Graduation date

  Spring 2014

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3R49GJ1X

• 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.