Figure 1.

Age-related changes of T_reg homeostasis. In young individuals T_regs are generated in the thymus and are released as “naïve-like” T_regs into circulation. After antigen-contact, T_regs develop into a “memory-like” phenotype. T_reg homeostasis is supported by homeostatic proliferation of “naïve-like” and “memory-like” T_regs as well as conversion of non-regulatory T-cells into T_regs. Telomere length and T-cell receptor diversity is higher in naïve-like compared to memory-like T_regs. After puberty thymic function is progressively lost and in aged individuals homeostatic proliferation of existing T_regs as well as conversion of non-regulatory T-cells into T_regs compensate for thymic failure to maintain T_reg pool. Due to ongoing homeostatic replication telomere length and T-cell receptor diversity of T_regs from elderly people are contracted compared to those from young individuals. Recurrent stimulation of T_regs might then lead to a status of “terminal-differentiation” with altered phenotype and function. T_reg regulatory T-cell, TCR … T-cell receptor.