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Nature Aging (2026) Cite this article
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Aging is associated with myeloid-biased hematopoiesis, which leads to the establishment of a pro-inflammatory microenvironment. We discovered that cytotoxic CD4+ T cells foster this process via the CCL5–CCR5 axis and found that the clinically approved CCR5 antagonist maraviroc can rebalance immunity in aged mice.
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References
Pellegrino, R. et al. Neutrophil, lymphocyte count, and neutrophil to lymphocyte ratio predict multimorbidity and mortality—results from the Baltimore Longitudinal Study on Aging follow-up study. Geroscience 46, 3047–3059 (2024). This paper reports that NLR is a predictor of all-cause mortality and multimorbidity based on a cohort of 1,769 aged participants.
Chongsathidkiet, P. et al. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat. Med. 24, 1459–1468 (2018). This paper reports sequestration of CD4+ T cells into the bone marrow of humans and mice with intracranial tumors.
Shi, K. et al. Bone marrow hematopoiesis drives multiple sclerosis progression. Cell 185, 2234–2247 (2022). This paper reports that autoreactive CD4+ T cells drive myelopoiesis during autoimmune neuroinflammation by secreting CCL5.
Hashimoto, K. et al. CD4 CTLs in supercentenarians: signs of adaptive expansion in healthy aging. Cell Rep. https://doi.org/10.1016/j.celrep.2026.117728 (2026). This paper shows that CD4+ CTLs expand in supercentenarians owing to persistent exposure to tumor antigens, potentially contributing to longevity through cancer suppression.
Hasegawa, T. et al. Cytotoxic CD4+ T cells eliminate senescent cells by targeting cytomegalovirus antigen. Cell 186, 1417–1431 (2023). This paper shows that senescent cells in the human skin upregulate HLA-II and human cytomegalovirus glycoprotein B, becoming targets of cytotoxic CD4+ T cells.
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This is a summary of: Gabandé-Rodríguez, E. et al. Cytotoxic CD4+ T cells induce age-associated myelopoiesis through CCL5–CCR5 signaling. Nat. Aging https://doi.org/10.1038/s43587-026-01209-9 (2026).
E.G.-R., G.S.-H. and M.M. used ChatGPT to help prepare their contribution to this Research Briefing.
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Cytotoxic CD4+ T cells support age-associated myelopoiesis. Nat Aging (2026). https://doi.org/10.1038/s43587-026-01241-9
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DOI: https://doi.org/10.1038/s43587-026-01241-9


