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Factors that regulate and maintain memory T cells

Dunne, Padraic J.; (2003) Factors that regulate and maintain memory T cells. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

A working immune system requires that T cells respond to foreign antigen, then return to a homeostatic level and remain poised to respond to subsequent re-challenge. In situations where tolerance is induced in T cells as a means of maintaining homeostasis, it is necessary that these cells survive activation-induced cell death (AICD) and under certain circumstances serve to suppress subsequent aggressive immune responses. The work carried out in this thesis shows that fibroblasts and type 1 IFN could not only rescue activated T cells from AICD but could also inhibit proliferation and maintain T cells in a quiescent state. It is also shown that the active anti-apoptotic mediator secreted by fibroblasts was IFN-β. Activated antigen-specific T cells rendered quiescent by fibroblasts, type I IFN and TGF-β1 retained their function and could be reactivated to proliferate. These mediators may therefore have an important role in the induction of quiescence in memory T cell populations after initial activation. To study this possibility the regulation of apoptosis in virus-specific memory CD8+ T cell populations was investigated using MHC class I tetramer staining. Throughout acute infection by Epstein Barr virus, virtually all antigen-specific T cells express a CD45RO phenotype. During chronic infection however, many cells revert to a CD45RA phenotype. Work carried out in this study shows that antigen-specific CD8+CD45RA+ revertant memory T cells were less susceptible to apoptosis than their CD45RO+ counterparts and represented a more stable memory population. These antigen-specific CD8+CD45RA+ T cells were not terminally differentiated and could be reactivated to proliferate. Neither fibroblasts, type I IFN nor TGF-β were capable of mediating CD45RO to CD45RA reversion in antigen-specific CD8+ T cells. Finally, results presented also show that fibroblasts and type I IFN could rescue T cells from AICD during anergy induction and these unresponsive cells were capable of suppressing equivalent responder T cell activation. Collectively these results suggest that type I IFN and TGF-β might have a central role in induction of immune quiescence through their effects at multiple points during activation of responsive T cells.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Factors that regulate and maintain memory T cells
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Health and environmental sciences; Memory; T cells
URI: https://discovery.ucl.ac.uk/id/eprint/10107412
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