ABSTRACT
The conserved lysosomal degradation pathway autophagy is now recognised as an essential cog in immune function. While functionally widespread in the innate immune system, knowledge of its roles in adaptive immunity is more limited. Although autophagy has been implicated in naïve T cell homeostasis, its requirement in antigen-specific T cells during infection was unknown. Using a murine model where the essential autophagy gene Atg7 is deleted in the T cell lineage, we have shown that autophagy is dispensable for effector CD8+ T cell responses, but crucial for the formation of memory CD8+ T cells. Here, we suggest reasons why autophagy might be important for the formation of long-lasting immunity. Like in the absence of autophagy, T cell memory formation during ageing is also defective. We observed diminished autophagy levels in T cells from aged mice, linking autophagy to immunosenescence. Importantly, T cell responses to influenza vaccination could be significantly improved using the autophagy-inducing compound spermidine. These results suggest the autophagy pathway as a desirable target to improve aged immunity and modulate T cell function.
