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.

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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.

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