The roles of Fas ligand in experimental autoimmune encephalomyelitis [electronic resource].

Liu, Tzu-Shang Thomas.
114 p.
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Mode of access: World Wide Web.
Experimental autoimmune encephalomyelitis (EAE) is a murine model of human multiple sclerosis. Previous studies have demonstrated that apoptosis occurs during the course of EAE and may thus be responsible for both the pathogenesis of and recovery from the disease. Fas and Fas ligand (FasL), a receptor-ligand pair of the tumor necrosis factor receptor and tumor necrosis factor family, have been shown to have important immunoregulatory roles. Thus, this project has investigated the role of the Fas-FasL interaction in EAE. We have used three different models to investigate the definitive mechanisms. First, through usage of mice with natural mutations in Fas and FasL, mice transgenic for a T-cell receptor specific for an epitope of an encephalitogenic protein (Tg+ mice), and recombinase-activation-gene knockout mice, we have been able to perform adoptive transfer experiments and conclude that FasL expressed by donor T cells, but not by non-lymphocytic cells, are important in induction of EAE. Second, through observations of spontaneous EAE in Tg+ mice, we have also discovered that incidence of spontaneous EAE surprisingly increases with the absence of Fas-FasL interaction. To resolve the conflicting results from the first two models, we used anti-FasL antibody to selectively block FasL at different stages of EAE. We determined that anti-FasL antibody increases EAE incidence when administered before the onset of disease but decreases mortality when administered after the onset of disease. Thus, FasL may play distinctly different roles during different phases of EAE, as it prevents disease during the initiation phase, increases disease during the inflammatory phase, and finally decreases disease during the recovery phase.
Source: Dissertation Abstracts International, Volume: 62-05, Section: B, page: 2246.
Adviser: Youhai Chen.
Thesis (Ph.D.)--University of Pennsylvania, 2001.
Local notes:
School code: 0175.
University of Pennsylvania.
Contained In:
Dissertation Abstracts International 62-05B.
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Restricted for use by site license.
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