Age-related autoimmunity

Abstract

Older persons have higher autoimmunity but a lower prevalence of autoimmune diseases. A possible explanation for this is the expansion of many protective regulatory mechanisms highly characteristic in the elderly. Of note is the higher production of peripheral T-regulatory cells.The frequent development of autoimmunity in the elderly was suggested to take place in part due to the selection of T cells with increased affinity to self-antigens or to latent viruses. These cells were shown to have a greater ability to be pro-inflammatory, thereby amplifying autoimmunity. During aging, thymic T-regulatory cell output decreases in association with the loss of thymic capacity to generate new T cells. However, to balance the above mentioned autoimmunity and prevent the development of autoimmune diseases, there is an age-related increase in peripheral CD4+ CD25highFoxP3+ T-regulatory cells. It remains unclear whether this is an age-related immune dysfunction or a defense response. Whatever the reason, the expansion of T-regulatory cells requires payment in terms of an increased incidence of cancer and higher susceptibility to infections.

Figure 1

Increased T-regulatory cell function in the elderly balances increased autoimmunity but increases the incidence of cancer and sepsis. (A) Autoantibodies are frequent in aged individuals because of increased tissue damage and apoptosis. (B) Aiming to balance this increased autoimmunity, peripheral Tregs become enhanced, suppressing both CD4 and CD8 T cell function, allowing the development of cancers and increasing susceptibility to infections. (C) Recurrent viral and bacterial infections stimulate pro-inflammatory cytokines, which are further stimulated by this expansion of Tregs. (D) Treg expansion in the elderly is followed by the increase of T-helper 17 cells and the persistence of chronic inflammation.