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Renick, Paul James Rhodes. M.S. in Microbiology and Immunology, Wright State University. 2002. CD28 Costimulation Requirement for Interferon-y Secretion by Natural Killer T cells During Hepatitis B Virus Infection. Natural Killer T cells (NKT cells) are a unique subset of lymphocytes that express natural killer (NK) and T cell receptors (TCR). The NKT cell population includes four separate subclasses. This paper will focus on Category I NKT cells which possess a canonical TCR receptor (Va14Ja281) that recognizes only hydrophobic antigens presented by CD1d molecules. These cells are believed to play an important regulatory role in immunity. A variety of disease conditions, including cancer, infections and Type I diabetes, are controlled by NKT cells. NKT cells are also capable of secreting large quantities of cytokines, namely interleukin-4 (IL-4) and interferon-gamma (IFN-y ). This ability to switch between Th1 (IFN-y ) and Th2 (IL-4) cytokines emphasizes the immunological regulatory role that these cells play. The mechanisms by which NKT cells select the cytokines they secrete are not well characterized. Blocking of CD28 by monoclonal antibodies or mutation of the CD28 gene impairs NKT cell s ability to secrete IFN-y in vitro. NKT cell of IFN-y secretion plays a significant role in the clearance of Hepatitis B virus (HBV) in a HBV transgenic mouse model. Abrogating or blocking expression of CD28 should significantly impair the ability of NKT cells to clear HBV infection. This thesis suggests a series of in vitro and in vivo experiments designed to test the role of CD28 in IFN-y secretion and HBV clearance in mice. |
