ROLE OF TYROSINE KINASE ITK IN SKIN ALPHA BETA T CELLS

Open Access
Author:
Bai, Yuting
Graduate Program:
Pathobiology
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
None
Committee Members:
  • Avery August, Thesis Advisor
Keywords:
  • skin
  • alpha beta T cells
  • Itk
Abstract:
ABSTRACT Itk, a member of the Tec family of tyrosine kinases, plays an important role in T cell development and differentiation. Itk regulates the development of αβ T cells such that positive selection and negative selection in the thymus are defective in absence of Itk. Itk is also important in the development and homeostasis of innate-like γδ T cells in the skin. In this thesis, we focused on skin αβ T cells and investigated the role of Tec kinase family members, Itk and Txk, in αβ T cell homoeostasis in skin T lymphocytes. For this purpose, we characterize αβ T cell populations in Itk deficient mice compared to WT mice. We found that the total cell number and the percentage of CD4+ T cells in Itk KO mice are significantly higher than those in WT mice. No significant difference was found in skin CD8+ T cells. We also used mice that express human Itk or murine Txk only in T cells on the Itk-/- background to determine whether this would rescue the difference we observe between WT and Itk KO mice. We found that T cell specific expression of both human Itk, and mouse Txk could restore the CD4+ population (percentage) in Itk KO mice. We also compared WT and Itk KO mice on a Balb/c background. The data did not show significant differences in the percentage of CD4+ and CD8+ T cells in these mice. In addition, we used CD44 and CD122 surface marker to characterize the phenotype of CD4+ and CD8+ T cells in skin and found that both WT and Itk KO have high CD44 expression, resembling activated or memory T cells. Thus this suggests that Itk may play an impotent role in development and or homeostasis of skin αβ T cells.