| Summary: | <p>CD8&plus; 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&plus; T cell homeostasis. When the essential autophagy gene <em>Atg7</em> is deleted in the T cell lineage (T-Atg7<sup>-/-</sup> mice), mice develop lymphopaenia leading to increased CD8&plus; T cell homeostatic proliferation. When CD8&plus; 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&plus; T cells utilise autophagy when responding to infection is currently unknown. We demonstrate that autophagy is dispensable for CD8&plus; T cell expansion, but loss of Atg7 results in the failure to establish CD8&plus; T cell memory to influenza and MCMV infection. Interestingly, CD8&plus; 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&plus; T cells from aged mice and the CD8&plus; 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.</p>
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