IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice
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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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Jackaman, Connie; Radley-Crabb, Hannah; Soffe, Z.; Shavlakadze, T.; Grounds, M.; Nelson, Delia (2013)Changes to innate cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), during aging in healthy or tumor-bearing hosts are not well understood. We compared macrophage subpopulations and MDSCs from healthy ...
Jackaman, Connie; Dye, Danielle; Nelson, Delia (2014)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 ...
Murine mesothelioma induces locally-proliferating IL-10<sup>+</sup>TNF-a<sup>+</sup>CD206<sup>-</sup>CX3CR1<sup>+</sup> M3 macrophages that can be selectively depleted by chemotherapy or immunotherapyJackaman, Connie; Yeoh, T.; Acuil, M.; Gardner, Joanne; Nelson, Delia (2016)© 2016 Taylor & Francis Group, LLC.We used a murine model to monitor changes to myeloid cell subsets, i.e., myeloid-derived suppressor cells (MDSCs), M1 macrophages that secrete pro-inflammatory cytokines and express CD40 ...