title: IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice.
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.
authors.affiliation: Immunology and Cancer Group, School of Biomedical Sciences, Curtin University, Perth, Western Australia, 6102, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Jackaman
authors.forename: D E
authors.initials: DE
authors.lastname: Dye
authors.forename: D J
authors.initials: DJ
authors.lastname: Nelson
mesh_terms: D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D019013:CD40 Antigens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008654:Mesothelioma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: D019013:CD40 Antigens; D007376:Interleukin-2
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