The impact of aging on regulatory T-cells

Age-related deviations of the immune system contribute to a higher likelihood of infections, cancer, and autoimmunity in the elderly. Senescence of T-lymphocytes is characterized by phenotypical and functional changes including the loss of characteristicT-cell surface markers, while an increase of stimulatory receptors, cytotoxicity as well as resistance against apoptosis is observed. One of the key mediators of immune regulation are naturally occurring regulatory T-cells (T-regs). T-regs express high levels of CD25 and the intracellular protein forkhead box P3; they exert their suppressive functions in contact-dependent as well as contact-independent manners. Quantitative and qualitative defects of T-regs were observed in patients with autoimmune diseases. Increased T-reg activity was shown to suppress antitumor and anti-infection immunity. The effect of aging on T-regs, and the possible contribution of age-related changes of the T-reg pool to the pathophysiology of diseases in the elderly are still poorly understood. T-reg homeostasis depends on an intact thymic function and current data suggest that conversion of non-regulatory T-cells into T-regs as well as peripheral expansion of existing T-regs compensates for thymic involution after puberty to maintain constant Treg numbers. In the conventional T-cell subset, peripheral proliferation of T-cells is associated with replicative senescence leading to phenotypical and functional changes. For T-regs, different developmental stages were also described; however, replicative senescence of T-regs has not been observed yet.