Thymic involution as an adaptive schedule for combating diverse pathogens.

Abstract

Diverse 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 value h(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 increase h(t). When pathogen encounter rates vary, h(t) decreases with age according to a power function. HighlightsO_LIThe thymus generates diverse naive T cells to recognize a wide range of pathogens. C_LIO_LIThymic involution is considered an adaptive strategy, factoring in maintenance cost. C_LIO_LIIf pathogen encounters are frequent, the rate starts high but quickly declines. C_LIO_LIThe rate increases with the pathogen risk and decreases with the thymic cost. C_LIO_LIIf pathogens vary in abundances, the rate decreases as a power function of age. C_LI