Thymic involution as an adaptive schedule for combating diverse pathogens

AbstractDiverse naive T cells, produced in the thymus, migrate to peripheral tissues and help suppress pathogens upon activation. As we age, the thymus shrinks, reducing both the supply and diversity of naive T cells, which increases the time required to establish immunity against new pathogens. This process, called thymic involution, is considered a form of aging. In this study, we explore whether thymic involution might be an adaptive strategy. Over time, the immune system accumulates memory cells, reducing the need for new naive T cells to combat unfamiliar pathogens. We examine how the optimal rate of naive T cell production,h(t), declines with age, taking into account the cost of maintaining thymic activity. When pathogen encounter rates are equal,h(t) decreases exponentially with age. As pathogen encounter rates rise, the initial valueh(0) increases, but the rate declines more rapidly with age, reducing overall production. A higher pathogen diversity, a greater cost of fighting new pathogens, and a lower cost of maintenance increaseh(t). When pathogen encounter rates vary,h(t) decreases with age according to a power function.HighlightsThe thymus generates diverse naive T cells to recognize a wide range of pathogens.Thymic involution is considered an adaptive strategy, factoring in maintenance cost.If pathogen encounters are frequent, the rate starts high but quickly declines.The rate increases with the pathogen risk and decreases with the thymic cost.If pathogens vary in abundances, the rate decreases as a power function of age.