The immune system must be controlled to prevent damage caused by inappropriate responses and extended inflammation. Regulatory T cells (Tregs), known to be generated by the thymus, must be maintained in the face of an ever-increasing human lifespan and associated thymic atrophy in order to protect the host, but whether they are maintained by expansion of pre-existing Tregs or conversion of conventional T cells is not yet known. There are known to be two subsets of FOXP3+ regulatory T cells: naive and memory cells, expressing CD45RA and CD45RO respectively. In this work the characteristics of CD45RA+ and CD45RO+ regulatory T cells were investigated in healthy adults. We found proliferative and phenotypic differences between the two subsets, and evidence that CD45RA+ Tregs can replenish the memory Treg pool on activation. It is, however, becoming more accepted that CD45RO+ Tregs are also likely to be composed of many cells that were converted externally to the thymus from conventional T cells, and our work suggests a mechanism for this conversion: anergy induction. We also found that the two Treg subsets are able to migrate to disparate tissues. Investigation of cutaneous immune responses in vivo revealed the presence of a significant proportion of Tregs, their numbers rising and falling in concordance with the number of conventional T cells. Finally, these investigations of Treg subsets were extended to investigate atopic dermatitis (AD), a hypersensitivity condition in which Tregs are implicated. We found significantly fewer CD45RA+ Tregs among AD patients, with unexpectedly low rates of turnover of these cells in AD skin, despite the presence of high proportions of CD4+FOXP3+ cells. Overall, the findings from this study imply disparate roles for CD45RA+ and CD45RO+ Tregs, and provide further evidence supporting a role for dysregulated regulatory T cell function in the pathogenesis of atopic dermatitis.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:564953 |
| Date | January 2010 |
| Creators | Booth, Nicola Jane |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/20160/ |
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