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Age‐related extrinsic factors affect naive CD4 T cell responses
Author(s) -
Maue Alexander,
Eaton Sheri,
Lanthier Paula,
Haynes Laura
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.663.13
Subject(s) - cd44 , immune system , il 2 receptor , interleukin 21 , t cell , immunology , adoptive cell transfer , biology , microbiology and biotechnology , in vitro , chemistry , biochemistry
Declines in immune function with age contribute to the reduced efficacy of vaccines in the elderly. Age‐related intrinsic defects in CD4 T cell function lead to reduced B cell helper activity. New studies have found extrinsic age‐related changes that influence the responses of naïve CD4 T cells. Aged mice displayed a significant increase in the number of CD4 T cells that express molecules associated with immune regulation as compared to young, including IL‐10, CD25, GITR and CTLA‐4. IL‐10 production resided almost exclusively within the CD62L lo subset of CD4 T cells. In vivo, naïve young transgenic (Tg) CD4 cells transferred into young or aged hosts exhibited decreased antigen‐specific expansion in aged hosts. This effect was attributable to host CD4 T cells, as in vivo CD4 depletion prior to adoptive transfer alleviated the impediment to proliferation. To determine this mechanism, an in vitro proliferation model was established in which young naïve Tg CD4 cells were primed in the presence of CD44 hi or CD44 lo polyclonal cells from young or aged mice. CD44 hi cells impeded dilution of CFSE within naïve cells regardless of donor age. Furthermore, IL‐10R blockade within CD44 hi ‐containing cultures abrogated the decreased proliferation of transgenic CD4 cells. Our results demonstrate that external factors in aged mice may act to inhibit naïve CD4 T cell responses.