Title page for ETD etd-52597-2116

Type of Document Master's Thesis
Author Bradley, Michael Joseph
Author's Email Address MjxB@aol.com
URN etd-52597-2116
Title Role of CD44, Fas Ligand, and Perforin in the Cytotoxicity Mediated by Natural Killer Cells
Degree Master of Science
Department Biology
Advisory Committee
Advisor Name Title
Holladay, Steven D.
Schurig, Gerhardt G.
Nagarkatti, Prakash S. Committee Chair
Nagarkatti, Mitzi Committee Co-Chair
  • Hyaluronate
  • Apoptosis
  • Natural Killer Cells
  • CD44
  • Perforin
  • Fas Ligand
Date of Defense 1997-06-16
Availability unrestricted
Two important mechanisms of lymphocyte-mediated cytotoxicity, one perforin based and the other Fas ligand (FasL) based, have been characterized recently. It has also been shown that CD44, an adhesion molecule, can participate in signaling cytotoxic activity of cytotoxic T lymphocytes (CTLs). In the current study we tested the hypothesis that activation of natural killer (NK) or lymphokine activated killer (LAK) cells induces the expression of FasL, perforin, and CD44 which together contribute towards increased cytolytic activity. To this effect, we used wild-type mice, perforin-knockout mice, and mice lacking a functional FasL. We observed that both interleukin-2 (IL-2) and Poly I:C triggered NK/LAK cells to lyse targets through the perforin- and FasL- pathways. In addition, Fas+ tumor targets were more susceptible to lysis by poly I:C and IL-2 activated NK/LAK cells when compared to Fas- targets. Furthermore, Fas- tumor cells injected subcutaneously into syngeneic mice could grow and induce tumors, whereas, Fas+ tumors were rejected. IL-2 treatment increased the CD44 expression on NK cells, which was responsible for the lysis of endothelial cells through its ligand, hyaluronate. Upregulation of perforin and FasL in activated NK/LAK cells may explain why such cells can kill a wide variety of tumor cells efficiently. On the other hand, activated NK/LAK cells express increase increased levels of CD44 and use this molecule to mediate cytotoxicity of endothelial cells, which may account for the vascular leak seen during IL-2 therapy.

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