Dietary restriction to optimize T cell immunity is an ancient survival strategy conserved in vertebrate evolution

Recent advances highlight a key role of transient fasting in optimizing immunity of human and mouse. However, it remains unknown whether this strategy is independently acquired by mammals during evolution or instead represents gradually evolved functions common to vertebrates. Using a tilapia model, we report that T cells are the main executors of the response of the immune system to fasting and that dietary restriction bidirectionally modulates T cell immunity. Long-term fasting impaired T cell immunity by inducing intense autophagy, apoptosis, and aberrant inflammation. However, transient dietary restriction triggered moderate autophagy to optimize T cell response by maintaining homeostasis, alleviating inflammation and tissue damage, as well as enhancing T cell activation, proliferation and function. Furthermore, AMPK is the central hub linking fasting and autophagy-controlled T cell immunity in tilapia. Our findings demonstrate that dietary restriction to optimize immunity is an ancient strategy conserved in vertebrate evolution, providing novel perspectives for understanding the adaptive evolution of T cell response.