Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605067
Title: Autoreactive CD8+ regulatory T cells in spondyloarthritis
Author: Jarvis, Lorna Beth
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2005
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Abstract:
There have been substantial advances in our understanding of the CD4+CD25+ regulatory T cell subset, but the possibility of an equivalent regulatory subset within the CD8+ T cell population has received less attention. In the course of studies investigating immunological abnormalities in patients with the inflammatory arthritis Ankylosing Spondylitis (AS), novel human CD8+ T cells that have a regulatory phenotype and function have been identified. CD8+/TCRαβ+ T cells were isolated from the peripheral blood of both AS patients and healthy donors and subsequently expanded as T cell lines using antilogous LPS activated dendritic cells. These lines contained IL-4 producing CD8+ T cells which were then cloned non-specifically by limiting dilution. Conventional CD8+ T cells are cytotoxic but these clones were not. They proliferated and produced cytokines in an autoreactive HLA class I restricted fashion; the cytokines produced included IL-4, IL-5 and TGFβ1, but not IFN-γ or IL-10. The clones expressed markers commonly associated with CD4+CD25+ regulatory T cells, including high levels of CTLA-4 and Foxp3. They suggested IFN-γ production and proliferation by CD4+ T cells in vitro in a cell contact dependent manner, which appeared to involve surface CTLA-4 since suppression could be blocked using an anti-CTLA-4 mAb. Increased numbers of these IL-4+ CD8+ T cells were found in AS patients’ PBMC stimulated directly ex vivo compared to healthy donors, and high numbers correlated with decreased numbers of pro-inflammatory IFN-γ producing T cells, suggesting they may actively regulate inflammation in vivo. Thus, human CD8+ regulatory T cells may be up-regulated in the peripheral blood under certain pathological conditions such as in response to chronic inflammation. AS is a remitting and relapsing inflammatory disease; therefore it is possible that these cells contribute to periods of remission by actively regulating inflammation in vivo.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.605067  DOI: Not available
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