Thymus Microenvironment: Maintenance, Ageing and Strategies for Thymus Regeneration Following Damage

The thymus is the major site of T-lymphocyte production. Nonlymphoid elements, referred to as the thymic stroma, create the thymic microenvironment required to govern differentiation, maturation and tolerance induction of haematopoietic precursors into immune-competent, nonautoreactive T cells. Thymic epithelial cells (TECs) are integral to thymopoiesis but are affected by ageing. From the onset of puberty, a proportional imbalance of TEC subpopulations coincides with a dramatic numerical loss of developing T cells. By middle-age numerical loss of TECs accompanies further loss of thymocytes. Ongoing functional impediment of bipotent thymic epithelial progenitor cells (TEPC) has been proposed as one possible underlying cause and is more apparent in males. As such, endogenous recovery following thymic damage, such as from chemotherapy, in middle-aged males relies heavily on proliferation of residual immature and mature TECs than through homeostatic differentiation of bipotent TEPC evident in middle-aged females. Various strategies have been proposed to enhance thymus recovery following cytoablative therapies; however, thus far, temporary suppression of sex hormone production appears to have the most wide-ranging impact on enhancing mature TEC replenishment and thymopoiesis.