The integrity of the thymus is essential for the output of T cells with diverse receptors, a point most dramatically demonstrated by the immunodeficiency in patients with DiGeorge syndrome (DGS)-a profound inborn immunodeficiency in which a 22q11 deletion results in defective third and fourth pharyngeal pouch development and thus hypoplasia of the thymus. The adaptive immune system relies on a diverse repertoire of receptor bearing lymphocytes allowing for the recognition of an untold number of potential pathogen targets and for the surveillance of cancerous mutated self-antigens. We will also discuss methods that are used to measure thymic function in patients and strategies that have been developed to boost thymic function. 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. 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. 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. TCR repertoire breadth is thus critical for not only coordinating the adaptive response against pathogens but also for mounting a response against malignancies. 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.
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