Homeostasis and function of regulatory T cells in aging

Abstract

A hallmark of aging is the progressive deterioration of immune function. Age-related immune suppression increases susceptibility to infectious diseases and cancer, significant causes of morbidity and mortality in the elderly. In particular, age-related T cell dysfunction is a major contributor to “immune-senescence”. Recently, it has become clear that the frequency of regulatory T cells (Treg) significantly increases in aged mice and humans. As Treg control the intensity of T cell responses, their accrual likely contributes to age-related immune dysfunction. This review will focus on mechanisms underlying Treg homeostasis and function in aging.

Aging disturbs the balance between effector and regulatory CD4+ T cells

“…Importantly, we distinguished CD45RA+CD25 int nTreg and CD45RA-CD25 high memT reg cells according to a state of the art flow cytometric gating strategy (Miyara et al, 2009) and confirmed their expression of the Treg transcription factor FOXP3, as well as their suppressive potential in vitro (Miyara et al, 2009;Booth et al, 2010). In earlier studies, aging was associated with either an increase or no change of circulating T reg cells (Raynor et al, 2012). Notable, a multitude of gating strategies was applied to identify T reg cells in earlier studies, without discriminating between nT reg and memT reg cells.…”

Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection

“…Aging has been associated with dysregulation of the immune system, which is then unable to fully respond to pathological insults (Plackett et al, 2004;Raynor et al, 2012). We thus evaluated how aging and chronic systemic infection influenced the concentrations of inflammatory cytokines and chemokines in both plasma and brain.…”

Enhanced renewal of regulatory T cells in relation to CD4+ conventional T lymphocytes in the peripheral compartment

“…[5][6][7] Despite permanent thymic emigration in the young or in the face of thymus involution during aging, the peripheral frequencies of Treg cells are physiologically kept stable throughout the majority of a lifetime, with significant increases being observed only in aged mice and humans. [8][9][10][11] This homeostatic balance implies a competition between recently thymus-emigrated (RTE) natural Treg cells and those Treg cell clones already resident in the periphery, which are generated by clonal expansion of natural Treg cells and/or post-thymic conversion to Treg phenotype, originating the so-called peripherally induced Treg.…”