# The effects of environmental oxygen on CD4+ T lymphocyte activation and responses

Clay, Elizabeth (2015). The effects of environmental oxygen on CD4+ T lymphocyte activation and responses. University of Birmingham. Ph.D.

 Preview
Clay15PhD.pdf
PDF - Accepted Version

## Abstract

The organs in which lymphocytes function are low in oxygen (<5% oxygen) and even lower oxygen levels may be more prevalent in inflammatory tissues. In this thesis the effects of environmental oxygen on human CD4+ memory T lymphocyte function $$in$$ $$vitro$$ have been investigated. The level of oxygen in normal air (21%) which historically has been used for most $$in$$ $$vitro$$ experiments with immune cells was found result in suboptimal responses of this cell type, especially with regards to proliferation. At physiologically more appropriate oxygen levels of 8.5%, optimal proliferation was observed which coincided with an increase in Th2-associated markers. At 3% oxygen, the average level found in the inflamed joint in rheumatoid arthritis, a more sustained pro-inflammatory response was observed. In 1% oxygen, cytokine production was not maintained over time paralleling observations of CD4+ T lymphocyte behaviour in both the tumour and chronic inflammatory environment. This comparison was further supported by the increased expression of the activation marker CD69 and the depression of CD4+ T lymphocyte proliferation. A model of reperfusion injury also highlighted the effect that varying oxygen levels can have on CD4+ memory T lymphocytes. Proximal T cell receptor signalling was found to be altered after equilibration at different oxygen levels, and preliminary experiments investigating the potential role that redox plays in regulating CD4+ memory T lymphocyte functions were performed. It is concluded that environmental oxygen levels significantly influence CD4+ memory T lymphocyte responses, have implications for their function in inflammatory sites $$in$$ $$vivo$$, and need to be considered when designing or interpreting $$in$$ $$vitro$$ experiments.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Supervisor(s):
Supervisor(s)EmailORCID
Young, StephenUNSPECIFIEDUNSPECIFIED
Wallace, GrahamUNSPECIFIEDUNSPECIFIED
Licence:
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Immunity and Infection
Funders: None/not applicable
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine
URI: http://etheses.bham.ac.uk/id/eprint/5795

### Actions

 Request a Correction View Item