What role does the thymus play in adults?

The Role of the Thymus in Adults

Despite age-related involution, the adult thymus continues to play a crucial role in maintaining immune competence through ongoing T-cell production and is essential for overall health.

Thymic Function in Adults

• The thymus remains functional well into the sixth decade of life, continuing to produce naive T lymphocytes that contribute to immune system optimization throughout adulthood 1
• Although the thymus decreases in size and cellularity with age (thymic involution), it maintains significant immune function in adults by producing new T cells that emigrate to the periphery 2
• Recent research demonstrates that adult thymus removal is associated with significantly higher all-cause mortality (8.1% vs 2.8% at 5 years) and increased cancer risk (7.4% vs 3.7%) compared to matched controls who underwent similar cardiothoracic surgery without thymectomy 3

T-Cell Production and Immune Competence

• Adult thymus continues to generate naive T cells, which can be measured through T-cell receptor excision circles (TRECs), with thymectomized adults showing significantly reduced production of both CD4+ and CD8+ lymphocytes compared to controls 3
• T-lymphocyte numbers in adults with thymic hypoplasia can reach levels similar to healthy adult controls through homeostatic proliferation, but naive T lymphocytes and TRECs remain reduced at all ages compared to age-matched controls 4
• The thymus contributes to maintaining a diverse T-cell receptor (TCR) repertoire in adults, which is essential for effective immune responses against pathogens, autoimmune disorders, and cancer 2

Impact of Thymic Involution on Health

• Thymic involution results in decreased naive T-cell emigration to the periphery, increased proportion of memory T cells, and a restricted T-cell receptor repertoire, leading to increased susceptibility to infectious diseases and higher risk for autoimmune disorders and cancers 2
• In adults with complete athymia, T-lymphocyte counts may appear normal due to increased B- and/or NK-cell numbers or oligoclonal T-lymphocyte expansions, but they have negligible TRECs and less than 5% of T lymphocytes displaying a naive phenotype 4
• Thymic involution contributes to immunosenescence through structural and functional loss affecting T-cell development, selection, and tolerance mechanisms 2

Clinical Implications

• Routine removal of the thymus in adults during surgical procedures should be reconsidered given the evidence of increased mortality and cancer risk following thymectomy 3
• Adults who undergo thymectomy show higher levels of proinflammatory cytokines in the blood, suggesting that the thymus plays a role in regulating systemic inflammation 3
• In patients with myasthenic crisis after thymectomy, careful monitoring of respiratory function and avoidance of medications that can worsen neuromuscular blockade are essential for management 5

Role in Immune Reconstitution

• The thymus plays a critical role in immune reconstitution following bone marrow transplantation and in HIV-1 infection, with age-dependent contributions of thymic emigrants and proliferation of post-thymic T cells to maintain the peripheral T cell pool 1
• In HIV-infected adults, thymic dysfunction occurs during disease progression, with decreases in TREC concentrations observed, though thymic recovery may be achieved in some patients with potent antiretroviral therapy 6
• There is a dynamic interplay between postnatal thymus output and peripheral T cell pool proliferation, with the thymus contributing more at younger ages but still playing an important role throughout adult life 1

Future Therapeutic Considerations

• The identification of thymic epithelial progenitor cells (TEPC) in the adult thymus offers potential for new therapies focused on regenerating the thymic microenvironment for diverse T cell reconstitution in elderly adults 7
• Intrathymic transforming growth factor-β (TGF-β) signaling may play an important role in TEPC activation and could be a target for thymus reactivation strategies 7
• Developing effective clinical treatments for thymus regeneration could help reconstitute peripheral T cell diversity in adults with severe immune deficiencies and potentially reverse age-related inflammatory conditions 7