Thymic regeneration in mice and humans following sex steroid ablation

Abstract

The thymus is the cradle of T-cell-mediated immunity. Normal thymic development ensures the export of a diverse repertoire of T-cells reactive against pathogens, foreign matter and tumours, and its role as the sole generator of αβTcells makes it a unique organ, indispensable for health. Although the thymus continues to produce T-cells throughout life, it undergoes progressive atrophy with age, restricting both the number and diversity of newly derived T-cells within the peripheral T-cell pool and compromising their ability to detect and respond efficiently to pathogens. This involution is most obvious from the onset of puberty and, accordingly, can be reversed with sex steroid ablation (SSA) therapy. Clinically, this is of paramount importance for patients with acquired immunodeficiencies, since the atrophied thymus cannot quickly export sufficient numbers of new T-cells to repopulate a depleted peripheral pool. Instead, patients are left dangerously susceptible to infection for extended periods. Reversible SSA promises to speed the time taken to immune recovery by rejuvenating the aged thymus and increasing T-cell output, with the potential to transform the clinical management of many major diseases with T-cell based aetiology.