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Title: Functional significance of CD4+ and CD8+ T lymphocytes in the immune response to murine gammaherpesvirus 68
Author: Robertson, Kevin Alasdair
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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Murine gammaherpesvirus 68 (MHV-68) is a natural pathogen of murid rodents and is closely related to Human Herpesvirus 8, Herpesvirus saimiri and Epstein Barr virus. In this study T lymphocyte responses to MHV-68 were examined in vitro and in vivo. In vitro work focused on developing a conventional assay to measure MHV-68-specific CTL activity. It was found that splenocytes from MHV-68-infected mice consistently lysed 'S11' cells, a B cell lymphoma line originally isolated from an MHV-68-infected mouse. All S11 cells are latently infected with MHV-68 and around 5% of these cells support viral replication. Treatment of S11 cells with the anti-viral drug, 4'-S-EtdU, is known to prevent lytic MHV-68 protein expression. 4'-S-EtdU-treated S11 target cells were killed by lymphocytes from infected mice. This indicates that the T lymphocytes responsible for killing S11 cells were specific for a latent antigen of MHV-68. No measurable cytolytic activity against any other target cell line, infected in vitro with MHV-68, was detected. S11 has been shown to divide and expand when implanted subcutaneously into nude (T cell-deficient) mice. S11 does not expand when implanted into normal, immunocompetent mice, implying that T lymphocytes play a key role in inhibiting tumour formation. In conclusion, MHV-68 infection of inbred laboratory mouse strains has potential to model immunological responses to primary gammaherpesvirus infection in humans. In addition, histopathology induced by the S11 cell line implanted into nude mice could provide insight into gammaherpesvirus-associated B lymphoproliferative disease in immunocompromised individuals.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available