Why does the thymus involute? A selection-based hypothesis

Thymic involution remains a fundamental mystery in immunology. Here we present an argument that this seemingly counterproductive behavior may have evolved to allow for peripheral selection of a T-cell repertoire during young-adult life, optimized for fighting infections and avoiding reaction to self. Age-associated decline in immune function may be viewed as an unfortunate side effect of this selective process. Thus, the key to understanding thymic involution might lie in a more quantitative understanding of T-cell homeostasis in the periphery.