Open AccessAging is associated with increased regulatory T ‐cell function
Author(s) -
Garg Sanjay K.,
Delaney Colin,
Toubai Tomomi,
Ghosh Amiya,
Reddy Pavan,
Banerjee Ruma,
Yung Raymond
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12191
Subject(s) - foxp3 , biology , regulatory t cell , cd86 , immunology , immune system , cell growth , il 2 receptor , microbiology and biotechnology , t cell , genetics
Summary Regulatory T‐cell (Treg, CD 4 + CD 25 + ) 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) C57 BL /6 mice. DNA from CD 4 + 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 DC s 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 CD 86 expression on DC s 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.