Affiliation:
1. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda Maryland USA
2. Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt‐Universität zu Berlin Berlin Germany
Abstract
SummaryThe thymus is the primary site of T‐cell development, enabling generation, and selection of a diverse repertoire of T cells that recognize non‐self, whilst remaining tolerant to self‐ antigens. Severe congenital disorders of thymic development (athymia) can be fatal if left untreated due to infections, and thymic tissue implantation is the only cure. While newborn screening for severe combined immune deficiency has allowed improved detection at birth of congenital athymia, thymic disorders acquired later in life are still underrecognized and assessing the quality of thymic function in such conditions remains a challenge. The thymus is sensitive to injury elicited from a variety of endogenous and exogenous factors, and its self‐renewal capacity decreases with age. Secondary and age‐related forms of thymic dysfunction may lead to an increased risk of infections, malignancy, and autoimmunity. Promising results have been obtained in preclinical models and clinical trials upon administration of soluble factors promoting thymic regeneration, but to date no therapy is approved for clinical use. In this review we provide a background on thymus development, function, and age‐related involution. We discuss disease mechanisms, diagnostic, and therapeutic approaches for primary and secondary thymic defects.
Subject
Immunology,Immunology and Allergy