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Aging‐Induced NF‐κB‐Dependent Alterations in T Cell Cytokines
Author(s) -
Huang MeiChuan,
Liao JiaJun,
Bonasera Stephen,
Longo Dan L.,
Goetzl Edward J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.663.6
Subject(s) - immunosenescence , cytokine , inflammation , immune system , t cell , cd28 , autoimmunity , proinflammatory cytokine , biology , interleukin 17 , chemistry , endocrinology , immunology , microbiology and biotechnology , medicine
Immunosenescence (IS) encompasses decreases in protective immune responses and increases in inflammation and autoimmunity. To elucidate cytokine components of IS, splenic CD4 T cells from 22 to 24 month‐old (old, O) mice and 6 to 10 week‐old (young, Y) mice were incubated for up to 4 days on adherent anti‐CD3 plus anti‐CD28 Abs with daily quantification of cytokines and their mRNAs. After 96 hr, T cells of O C57BL/6 and CBA mice generated more IL‐17 (up to 20‐fold) and IL‐6 (up to 3‐fold) than those of Y mice, T cells of Y mice generated up to 5‐fold more IL‐21 than those of O mice, and no difference was found for IFN‐γ. At 24 hr, cytokine mRNA levels paralleled 96 hr cytokine concentrations. Naïve (CD62L‐high) CD4 T cells from O mice on Abs with TGF‐β, IL‐1, IL‐6 and IL‐23 expressed more IL‐17 mRNA and IL‐17 at days 3 and 5 than those of Y mice. The nuclear levels of NF‐κB were lower in CD4 T cells of O than Y mice, but further decreases of their NF‐κB by BAY11‐7082 reduced IL‐17 and IL‐6 levels to those of CD4 T cells from Y mice. High reversibility of enhanced generation of T cell cytokines in IS suggests specific therapy for aging‐induced inflammation. (NIH grant RO‐1 HL31809)