How memory cells form and how they survive are pertinent, unanswered questions in the field of immunology. T cell memory develops following an adaptive immune response, which is initiated in secondary lymphoid organs. This response involves T cell proliferation, effector cell differentiation and the generation of memory cells. It has proved difficult to study CD4 T cell responses due to the problems of tracking the small number of antigen specific T cells. MHC class II tetramers, which bind to the T cell receptor of responding T cells, enable the identification of antigen specific CD4 T cells and, therefore, can be used to track memory cells. The importance of this system lies in the physiological number of precursor cells, providing a more realistic system to study CD4 T cell immunology than T cell receptor transgenic studies. In this PhD, MHC class II tetramers have been used to track endogenously generated, antigen specific CD4 T cells <i>ex vivo</i>. This has enabled the tracking of a CD4 T cell response from early activation, into memory, and during recall responses. Long-term studies have been carried out to determine the survival of memory cells in both the absence and presence of antigen, and to describe the phenotype of these cells. Furthermore, this system has been used to answer questions about the requirements of both naïve and memory cells for the costimulatory signals necessary for activation and proliferation. Specifically, the requirements for the interactions between the costimulatory molecules, CD40L-CD40 and ICOS-B7h, have been examined by comparing T cell priming, memory cell generation and recall responses in wild-type and knockout mice.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:654403 |
| Date | January 2005 |
| Creators | MacLeod, Megan Kathryn Louise |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/12522 |
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