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The kinetics of T cell responses.

Allan, M.J.; (2005) The kinetics of T cell responses. Doctoral thesis , University of London. Green open access

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The proliferation of T cells in response to an antigenic stimulus is a vital component of the adaptive immune response. Recently it has been demonstrated that, following a brief encounter with antigen, T cells enter a developmental program that can produce a full response in the absence of further antigenic stimulation. The striking similarity of T cell kinetics in different hosts in response to different stimuli demonstrates that the program strictly regulates cell number. Although T cells are receptive to a diverse range of modulatory signals, this invariance of key aspects of their kinetics suggests that regulation of cell number may be produced by a single mechanism. The first aim of this thesis is to identify the most plausible mechanism that could regulate the T cell kinetics during an acute response. Using an ODE compartmental model to keep track of the number of cells in each generation, the predictions of a number of plausible regulatory mechanisms are compared to experimental data to determine the potential of each to regulate cell number. One revealing conclusion is that all successful mechanisms progressively increase the apoptosis rate during the response. The most plausible mechanisms are then further assessed to determine which produces the least wasteful response (in terms of unnecessary T cell death). It is concluded that the most plausible mechanism is one that progressively increases death rates and decreases division rates. The second aim of this thesis is to investigate how the programmed nature of the regulatory mechanism affects the outcome of infection. Two aspects of the outcome of infection are considered: the size of the generated memory population, and the success, or otherwise, of pathogen clearance. The previous compartmental model is extended to incorporate the formation of memory cells, and the impact of the pro gram parameters on the final memory size following an acute infection is established. Situations when the pathogen can persist beyond the acute phase are then considered, and a discrete-time population model is developed to predict the long-term behaviour of the response. It is found that if the developmental program always produces a net increase in cell population size then pathogen clearance is guaranteed. A further conclusion is that during this long-term infection the sensitivity of the specific memory cells to re-stimulation diminishes.

Type: Thesis (Doctoral)
Title: The kinetics of T cell responses.
Identifier: PQ ETD:591828
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest
UCL classification:
URI: https://discovery.ucl.ac.uk/id/eprint/1444522
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