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    IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice

    Access Status
    Fulltext not available
    Authors
    Jackaman, Connie
    Dye, Danielle
    Nelson, Delia
    Date
    2014
    Type
    Journal Article
    
    Metadata
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    Citation
    Jackaman, C. and Dye, D. and Nelson, D. 2014. IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice. Age. 36: pp. 1315-1328.
    Source Title
    Age
    DOI
    10.1007/s11357-014-9655-y
    ISSN
    1574-4647
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/3766
    Collection
    • Curtin Research Publications
    Abstract

    The role of macrophages and their interactions with T cells during aging is not well understood. We determined if activating elderly-derived macrophages could rescue age-related and tumor-induced T cell dysfunction. Healthy elderly (18–24 months) Balb/c contained significantly more splenic IL-10-secreting M2-macrophages and myeloid-derived suppressor cells than young (6–8 weeks) mice. Exposure to syngeneic mesothelioma or lung carcinoma-conditioned media polarized peritoneal macrophages into suppressive M2-macrophages regardless of age. Tumor-exposed, elderly, but not young-derived, macrophages produced high levels of IL-4 and could not induce T cell IFN-γ production. We attempted to rescue tumor-exposed macrophages with LPS/IFN-γ (M1 stimulus) or IL-2/agonist anti-CD40 antibody. Tumor-exposed, M1-stimulated macrophages retained high CD40 expression, yet TNF-α and IFN-γ production were diminished relative to non-tumor-exposed, M1-stimulated controls. These macrophages induced young and elderly-derived T cell proliferation however, T cells did not secrete IFN-γ. In contrast, tumor-exposed, IL-2/CD40-stimulated macrophages rescued elderly-derived T cell IFN-γ production, suggesting that IL-2/CD40-activated macrophages could rescue T cell immunity in aging hosts.

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