Aging is associated with increased regulatory T‐cell function

Abstract

Regulatory T-cell (Treg, CD4+CD25+) dysfunction is suspected to play a key role in immune senescence and contributes to increased susceptibility to diseases with age by suppressing T-cell responses. FoxP3 is a master regulator of Treg function, and its expression is under control of several epigenetically labile promoters and enhancers. Demethylation of CpG sites within these regions is associated with increased FoxP3 expression and development of a suppressive phenotype. We examined differences in FoxP3 expression between young (3–4 months) and aged (18–20 months) C57BL/6 mice. DNA from CD4+ T cells is hypomethylated in aged mice, which also exhibit increased Treg numbers and FoxP3 expression. Additionally, Treg from aged mice also have greater ability to suppress effector T-cell (Teff) proliferation in vitro than Tregs from young mice. Tregs from aged mice exhibit greater redox remodeling–mediated suppression of Teff proliferation during coculture with DCs by decreasing extracellular cysteine availability to a greater extent than Tregs from young mice, creating an adverse environment for Teff proliferation. Tregs from aged mice produce higher IL-10 levels and suppress CD86 expression on DCs more strongly than Tregs from young mice, suggesting decreased T-cell activity. Taken together, these results reveal a potential mechanism of higher Treg-mediated activity that may contribute to increased immune suppression with age.

Dysregulation of Toll-Like Receptor 7 Compromises Innate and Adaptive T Cell Responses and Host Resistance to an Attenuated West Nile Virus Infection in Old Mice

“…Higher levels of peripheral CD4 ϩ CD25 ϩ Foxp3 ϩ "natural" Tregs after infection protect young adult mice against severe WNV disease (52). Although aging is associated with increased Treg function (40,53), we noted lower number of Tregs in old mice than in young mice upon WNV NS4B-P38G mutant infection. CD4 ϩ Treg expansion was also compromised in NS4B-P38G-infected TLR7 Ϫ/Ϫ mice.…”

“…Accumulating evidence shows that immune suppression increases with age (40,41). Therefore, we investigated whether R848 decreased the immunosuppressive effects on T cells in old mice.…”

Age-Dependent Changes in Regulatory T Lymphocyte Development and Function: A Mini-Review

“…Treg isolated from young adult and old mice display similar suppressive activity in vitro [33] . It has even been described that old Treg, by producing more IL-10 and by inducing a greater down-regulation of costimulatory molecules on DC, are better suppressors than Treg from young adult mice [34] . Despite their intact suppressive activities, Treg from old mice display a different phenotype than Treg isolated from young adult mice.…”

Senescencia del sistema inmune y alteraciones relacionadas con el asma

“…Por otra parte, estudios en animales han mostrado cambio en su función; los linfocitos TCD4 FoxP3 de ratones viejos producen más IL-10 y suprimen a la molécula CD80 (B7-1) en células dendríticas, lo que aumenta la supresión inmune. 55 Células madre Las células madre del mesénquima provenientes de ancianos, contrario a lo que sucede con las de jó-venes, no son capaces de diferenciarse in vitro a células neuroectodérmicas, 56 lo que limita la utilización de células autólogas de personas mayores, para reemplazo o regeneración de tejidos, más aún su donación.…”