Cytokines in the immunopathogenesis of murine graft-versus-host disease

Williamson, Eilidh (1997) Cytokines in the immunopathogenesis of murine graft-versus-host disease. PhD thesis, University of Glasgow.

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Abstract

Murine models of graft-versus-host disease (GvHD) provide important information relevant to clinical bone marrow transplantation (BMT), as well as to other types of T cell-mediated pathology. The nature of the GvHD which develops in (C57BL/6 X DBA/2)F1 (BDF1) mice injected with parental lymphocytes is dependent on whether C57B1/6 (B6) or DBA/2 parental donor cells are used. BDF1 mice injected with B6 donor cells (B6 => BDF1) develop an acute GvHD with early lymphoid hyperplasia and NK cell activation, followed by immunosuppression, activation of anti-host cytotoxic T lymphocytes (CTL), weight loss and early death. In contrast, BDF1 mice given DBA/2 donor cells (DBA/2 => BDF1) exhibit a chronic, stimulatory GvHD, characterised by B cell hyperreactivity, autoantibody production and immune complex-mediated glomerulonephritis (ICGN). Previous studies have shown that the distinct forms of GvHD in BDF1 recipient mice are associated with different patterns of cytokine production. Whereas acute GvHD is characterised by production of high levels of Th1 cytokines, chronic GvHD is associated with a preferential Th2 response. Therefore, it was suggested that the two forms of GvHD may reflect differential activation of distinct subsets of CD4+ T helper (Th) cells. However, when and why such T cell polarisation should occur has remained unclear. A number of recent studies have demonstrated that cytokines produced by cells of the non-specific immune system during the early phase of an immune response can strongly influence the type of specific response which develops subsequently. The main aim of this thesis was to explore the role of these early immune mediators in determining the outcome of the GvHD in BDF1 mice. These studies of the cellular and molecular interactions involved in murine GvHD have implications for understanding the pathogenesis of clinical GvHD and the development of specific therapy following BMT. In addition, they provide an important insight into the regulation of immune responses during other immunologically-mediated diseases.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Mowat, Prof. Allan and Garside, Prof. Paul
Date of Award: 1997
Depositing User: Mrs Marie Cairney
Unique ID: glathesis:1997-40906
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 07 Jan 2019 16:11
Last Modified: 07 Jan 2019 16:11
URI: http://theses.gla.ac.uk/id/eprint/40906
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