Single-cell map of the healthy human immune system across the lifespan reveals unique infant immune signatures

We profiled PBMCs from 167 healthy individuals (ages 2 months to 105 years): infants (n=36), children (n=26), adolescents (n=20), young adults (n=24), middle‑aged (n=16), older adults (n=33) and oldest old (n=12) using scRNA‑seq and snATAC‑seq (n=23). MAIT and γδ T cells showed a “rise and fall” pattern, rising in childhood, peaking in young adulthood, and declining with age.

Conventional CD8⁺ T cells were most profoundly altered with age, with decreasing naïve and increasing GZMK⁺ and TEMRA cells. The oldest old had increased TEMRA, adaptive NK, and KLRF1⁺ γδ T cells. Infants showed increased CD16⁺ monocytes and pDCs, constitutive interferon‑stimulated gene expression, and expanded SOX4⁺ naïve T cells.