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Title page for ETD etd-03182005-135908


Type of Document Dissertation
Author Sundrud, Mark Scott
Author's Email Address mark.sundrud@vanderbilt.edu
URN etd-03182005-135908
Title Molecular determinants of human T cell differentiation and host-pathogen interaction
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Wasif Khan Committee Chair
Derya Unutmaz Committee Member
Eugene Oltz Committee Member
Luc Van Kaer Committee Member
Mark Decaestecker Committee Member
Keywords
  • Naive T cell
  • Memory T cell
  • H. pylori
  • transcription factor
  • CCR5
  • HIV
  • effector memory
  • central memory
  • cytokines
  • chemokine receptor
  • GATA-3
  • T-bet
  • Th2
  • T cells
  • Th1
Date of Defense 2005-02-11
Availability unrestricted
Abstract
The differentiation of naive T helper (Th) cells into effector/memory subsets and their interaction with invading pathogens ultimately determines the outcome of infectious human diseases. The research detailed herein is aimed to delineate the transcriptional regulation of human Th cell differentiation and to further understand how these cells interact with microbial pathogens. Utilizing a lentiviral transduction system, we genetically modify primary human Th cells to further elucidate the roles of T-bet and GATA-3 during human Th cell differentiation. Furthermore, we describe how two important human pathogens, human immunodeficiency virus (HIV)-1 and Helicobacter pylori (H. pylori), usurp or perturb Th cell function, possibly contributing to their evasion of human immune responses. Our results lend novel insight into the regulation of human Th cell differentiation, function and interaction with pathogens. Moreover, this work has implications in the development of novel therapeutic strategies to manipulate Th cell function during infectious diseases or immunopathologies.
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