Dynamics of thymus function and T cell receptor repertoire breadth in health and disease

Granadier, David; Iovino, Lorenzo; Kinsella, Sinéad; Dudakov, Jarrod A.

T cell recognition of unknown antigens relies on the tremendous diversity of the T cell receptor (TCR) repertoire; generation of which can only occur in the thymus. TCR repertoire breadth is thus critical for not only coordinating the adaptive response against pathogens but also for mounting a response against malignancies. However, thymic function is exquisitely sensitive to negative stimuli, which can come in the form of acute insult, such as that caused by stress, infection, or common cancer therapies; or chronic damage such as the progressive decline in thymic function with age. Whether it be prolonged T cell deficiency after hematopoietic cell transplantation (HCT) or constriction in the breadth of the peripheral TCR repertoire with age; these insults result in poor adaptive immune responses. In this review, we will discuss the importance of thymic function for generation of the TCR repertoire and how acute and chronic thymic damage influences immune health. We will also discuss methods that are used to measure thymic function in patients and strategies that have been developed to boost thymic function.