IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice
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-sec...
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| Format: | Journal Article |
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Springer Netherlands
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/3766 |
| _version_ | 1848744321794179072 |
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| author | Jackaman, Connie Dye, Danielle Nelson, Delia |
| author_facet | Jackaman, Connie Dye, Danielle Nelson, Delia |
| author_sort | Jackaman, Connie |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T05:59:37Z |
| format | Journal Article |
| id | curtin-20.500.11937-3766 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T05:59:37Z |
| publishDate | 2014 |
| publisher | Springer Netherlands |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-37662018-03-29T09:05:22Z IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice Jackaman, Connie Dye, Danielle Nelson, Delia T cell Immune restoration Elderly Macrophage Cancer immunotherapy Innate immunity 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. 2014 Journal Article http://hdl.handle.net/20.500.11937/3766 10.1007/s11357-014-9655-y Springer Netherlands restricted |
| spellingShingle | T cell Immune restoration Elderly Macrophage Cancer immunotherapy Innate immunity Jackaman, Connie Dye, Danielle Nelson, Delia IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice |
| title | IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice |
| title_full | IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice |
| title_fullStr | IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice |
| title_full_unstemmed | IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice |
| title_short | IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice |
| title_sort | il-2/cd40-activated macrophages rescue age and tumor-induced t cell dysfunction in elderly mice |
| topic | T cell Immune restoration Elderly Macrophage Cancer immunotherapy Innate immunity |
| url | http://hdl.handle.net/20.500.11937/3766 |