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Title: The role of autophagy in CD8plus T cell immunity
Author: Puleston, Daniel
ISNI:       0000 0004 5362 7712
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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CD8+ T cells form a crucial arm of the adaptive immune system and act as sentinels against infection and cancer. The role of autophagy, a major lysosomal degradation pathway, in T cell biology is currently limited. Here, we show that autophagy is required for naïve CD8+ T cell homeostasis. When the essential autophagy gene Atg7 is deleted in the T cell lineage (T-Atg7-/- mice), mice develop lymphopaenia leading to increased CD8+ T cell homeostatic proliferation. When CD8+ T cells encounter antigen, they undergo an initial expansion before contracting, leaving behind a population of long-lived memory cells that provide long-lasting immunity. How CD8+ T cells utilise autophagy when responding to infection is currently unknown. We demonstrate that autophagy is dispensable for CD8+ T cell expansion, but loss of Atg7 results in the failure to establish CD8+ T cell memory to influenza and MCMV infection. Interestingly, CD8+ T cell memory becomes defective in old age, although the cellular mechanism for this is largely unknown. Here, aged mice were shown to exhibit defective CD8+ T cell expansion and memory formation to immunisation. Autophagy levels were diminished in antigen-specific CD8+ T cells from aged mice and the CD8+ T cell response of old mice to vaccination could be rejuvenated in an autophagy-dependent manner using the compound spermidine. These results suggest that targeting of the autophagy pathway might be beneficial as a route to effective T cell modulation and enhanced immunity to infection and vaccination.
Supervisor: Simon, Katja Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Immunochemistry ; Cell Biology (see also Plant sciences) ; Immunology ; Infectious diseases ; immunity ; autophagy ; T cells ; ageing ; influenza ; infection ; vaccination ; lymphocytes