The Role of T Regulatory Cells in Immune Senescence
T regulatory cells (Treg), defined by the transcription factor FoxP3, play an essential role in immune regulation and are required throughout life. Treg are generated either directly from the thymus or via peripheral T cells which acquire regulatory phenotype when activated in the presence of factors such as TGFβ. The relative contribution of these two populations over the life course is unclear. The number of T regulatory cells increases with age in both mice and humans, and CD4+FoxP3+ cells represent around 4.4% and 5.8% of the CD4+ repertoire in younger (<30 years) and older people (>70 years), respectively. This may relate to increased peripheral conversion from effector cells, methylation at regulatory elements of FoxP3, or reduced expression of apoptotic proteins such as Bim. Importantly, the function of T regulatory cells does not appear to deteriorate with age. There is increasing interest in the potential role of Treg cells in the development of immune senescence. Antibody-mediated CD25 cell depletion can improve immune responses and clinical protection to influenza challenge in aged mice, but translation of these findings to humans has not yet been undertaken. Depletion of Treg cells is a therapeutic aim in the treatment of cancer but complicated by the development of autoimmunity. In addition, cohort studies suggest that increased numbers of regulatory cells may be associated with improved overall survival in older people. T regulatory cells play an essential and complex role in the immune homeostasis of older people, but optimal approaches to therapeutic manipulation are currently uncertain.
KeywordsT regulatory FoxP3 Aging Immune senescence Autoimmunity
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