Cytotoxic CD4(+) T cells induce age-associated myelopoiesis through CCL5-CCR5 signaling.

Cytotoxic CD4+ T cells in aged mice drive myelopoiesis and increase the neutrophil-to-lymphocyte ratio via CCL5–CCR5 signaling, with CCR5 blockade normalizing these changes.

• Why it matters: Age-associated hematopoietic skewing raises the neutrophil-to-lymphocyte ratio, which predicts all-cause mortality in older adults, but the underlying mechanism is unclear.
• What they did: The study used aged mouse models to show T cell receptor–dependent mitochondrial stress and STING activation upregulate CCL5 in CD4+ T cells, while hematopoietic stem and myeloid progenitors increase CCR5; Ccr5 ablation or maraviroc treatment tested causality.
• The result: Removing CCR5 in hematopoietic progenitors mitigated T cell–induced myeloid skewing, and pharmacologic CCR5 inhibition with maraviroc normalized myelopoiesis, reduced neutrophils, and improved aging-related biomarkers and functional outcomes in aged mice.

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