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Title page for ETD etd-07222008-173518


Type of Document Dissertation
Author Kim, Sungjune
Author's Email Address sungjune.kim@vanderbilt.edu
URN etd-07222008-173518
Title Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Henry E. Ruley Committee Chair
Guoqiang Gu Committee Member
Louise A. Rollins-Smith Committee Member
Luc Van Kaer Committee Member
Wasif N. Khan Committee Member
Keywords
  • hyporesponsiveness
  • e.coli
  • listeria
  • invariant
  • NKT
  • natural killer t
  • anergy
  • Host-bacteria relationships
  • T cells -- Therapeutic use
Date of Defense 2008-06-17
Availability unrestricted
Abstract
The pathogen-host interaction between bacteria and invariant NKT (iNKT) cells is explored in this dissertation. iNKT cells are innate-like lymphocytes that recognize glycolipid antigens in the context of the MHC class I–like antigen-presenting molecule CD1d. The impact of bacterial infection on the phenotype and function of these cells have been carefully dissected in this dissertation, and the results indicate that mouse iNKT cells activated in vivo by multiple bacterial microorganisms, or by bacterial LPS or flagellin, become unresponsive to subsequent activation with alpha-GalCer. This hyporesponsive phenotype of iNKT cells required IL-12 expression and was associated with changes in the surface phenotype of these cells, reduced severity of concanavalin A–induced hepatitis, and alterations in the therapeutic activities of alpha-GalCer. These findings may have important implications for the development of iNKT cell–based therapies.
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