Thymus involution and regeneration: two sides of the same coin?

In vertebrates, the thymus is the main site of T cell development. The thymus reaches its maximum output during adolescence, after which it shrinks and generates fewer and fewer T cells. Physiological age-related involution of the thymus and failure to recover after injury are associated with impaired cellular immunity; hence, there is considerable interest in developing strategies to combat these deficiencies. In this Opinion article, we briefly review the phylogenetic and ontogenetic hallmarks of thymus development and function, and we discuss experimental models of impaired thymopoiesis and the molecular mechanisms of thymopoietic recovery. At each stage of the discussion we highlight the major gaps in our current knowledge.