Thymus function, ageing and autoimmunity

We suggest that the thymus is the critical timekeeper in the ageing process with respect to immune responses. Because the thymus involutes asymmetrically, a clonal imbalance occurs with ageing since the proportion of autoantigen-specific helper/inducer T cells increases relative to the number of autoantigen-specific regulatory T cells. As a result, circulating autoantibody levels rise with age. On the other hand, nonspecific immunoregulatory mechanisms increase with age. As the thymic cortex atrophies, the response to foreign antigens declines, whereas the response to self-antigen rises, generating the ageing paradox.