Thymus

The thymus is a bilobed organ in the anterior mediastinum where T cells are made competent. Thymocytes arriving from bone marrow rearrange their receptor genes and are tested. In the cortex, positive selection keeps only cells engaging self-MHC with modest affinity; the rest die by neglect. In the medulla, negative selection deletes cells binding self-peptide too strongly, a process depending on the AIRE transcription factor, which drives promiscuous expression of tissue-restricted antigens. Many regulatory T cells are generated here as well.

Two natural experiments show how much this matters. AIRE mutations cause autoimmune polyendocrine syndrome type 1, with autoimmunity against multiple endocrine organs, and thymic aplasia in 22q11.2 deletion syndrome produces profound T-cell deficiency. The organ reaches its greatest functional mass in childhood and then involutes, tissue progressively replaced by fat, so thymic output measured by T-cell receptor excision circles falls steadily through adult life.

Falling output is not falling T-cell numbers. Adults maintain the peripheral compartment largely by homeostatic proliferation of existing cells, which keeps counts stable while narrowing repertoire diversity and shifting the balance from naive toward memory. That underlies weaker vaccine responses in older adults, and explains why a normal lymphocyte count at seventy is compatible with a degraded ability to respond to something new.

Thymic regeneration is an active research question and a marketing opportunity, easily confused. The most-cited human result, a small study in nine men reporting regeneration on imaging after growth hormone with two other agents, is a hypothesis-generating pilot with no control arm. Products promising thymus support offer no measurement of thymic output at all.