In vitro studies on immunoregulation with special reference to rheumatoid arthritis

Bellamy, Nicholas (1981) In vitro studies on immunoregulation with special reference to rheumatoid arthritis. MD thesis, University of Glasgow.

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This thesis is based on studies conducted between 1979 and 1981 at the University of Western Ontario, London, Canada. Although considerable advance has been made in recent years in quantitation of various aspect of the immune response in rheumatoids, and in dissecting mechanisms by which the response is regulated in healthy individuals, there is a relative lack of information regarding immunoregulation in rheumatoid arthritis. A series of comparative studies were planned to examine quantitative and qualitative aspects of immunoregulation in patients with rheumatoid arthritis and normal healthy individuals. The introductory chapters of the thesis review certain aspects of rheumatoid arthritis and immunology, immunoregulation in normal individuals and the immunopathogenesis of rheumatoid arthritis. Subsequent chapters report the collection, standardization, modification and application of study methods and discuss the results of serial studies. For the functional studies, a modified reverse hemolytic plaque forming cell assay was used to measure immunoglobulin synthesis by B lymphocytes in cultures containing combinations of B and T lymphocytes. In this assay system responses (Studies 1-5) were shown to be related to culture duration, concentration and batch of pokeweed mitogen, source of foetal calf serum and the dose of irradiation used to manipulate the T cell help/suppression balance. In Study 6 immunoregulation was examined by selectively destroying T suppressor cells with optimal dose radiation prior to coculture with B cells, and in Study 7 by selectively removing T suppressor cells using a chicken rosette assay which depleted T cell suspensions of cells bearing Fc receptors for IgG (Tgamma cells) prior to coculture. In normal subjects, coculture of B cells with T cells enhanced the PFC (plaque forming cell) response, which was further increased when T cells were either irradiated at optimal dosages (T3200) depleted of Tgamma cells (T nongamma) prior to coculture - a response consistent with an effective reduction of suppressor T cell activity. In marked contrast, while rheumatoid T cells were capable of enhancing the response of rheumatoid B cells to an equivalent degree as in controls, the additional augmentation seen when B cells were co-cultured with T3200 or T nongamma cells was absent in almost all rheumatoids. These observations were interpreted as indicating a functional and/or numerical deficiency in one or several subsets of mononuclear cells, but were not consistent with a pure dysfunction or reduction in the number of suppressor T cells alone. While abnormalities in T suppression in rheumatoid arthritis have recently been reported, the co-existence of other immunoregulatory abnormalities has not been examined. It was also demonstrated that the controversial Tgamma cell population had suppressor activity and that the radiosensitive suppressor cell and the Tgamma cell were related. Finally, the restricted PFC response in rheumatoids was not found to be related to the number of Tgamma cells, which was normal. Prior to undertaking additional functional studies, lymphocyte suspensions were examined for their content of monocytes, Ia+ T cells and OKT4+, OKT5+ cells, since a numerical abnormality would have provided a simple explanation for the differences. (Abstract shortened by ProQuest.).

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: D A Bell
Keywords: Immunology
Date of Award: 1981
Depositing User: Enlighten Team
Unique ID: glathesis:1981-72478
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06

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