Age- and disease-related decline in immune function: an opportunity for "thymus-boosting" therapies

The thymus is the site of production of mature T lymphocytes and thus is indispensable for the development and maintenance of the T cell-mediated arm of the immune system. Thymic production of mature T cells is critically dependent on an influx of bone marrow-derived progenitor T cells that undergo replication and selection within the thymus. Thymus cellularity and thymic hormone secretion reach a peak during the first year of life and then decline gradually until the age of 50-60 years, a process known as "thymic involution." A rapid reduction of thymus cellularity occurs in young patients following injuries, chemotherapy, and other forms of stress. The mechanisms underlying the involution process appear to be dependent on factors intrinsic to the thymic tissue, such as the local production of cytokines and chemoattractants, promoting the recruitment, growth, and differentiation of bone marrow-derived T cell progenitors in the thymus, as well as extrinsic factors, such as systemic levels of endocrine hormones and mediators released by intrathymic nerves of the autonomic nervous system. Knowledge of these factors provides a rational basis for the development of an approach based on tissue engineering that could be used to provide either temporary or permanent reconstitution of thymic function.