Early life is essential for establishing memory T cells, which rapidly populate mucosal sites during infancy, although these nascent memory T cells are less protective than their adult counterparts. Here we used single-cell RNA sequencing of resting and CD3+CD28 antibody-stimulated T cells from lymphoid and mucosal tissues of infant (2–9 months) and adult (40–63 years) organ donors to investigate age-dependent mechanisms for functional regulation of human memory T cells.
Infant CCL5 + effector memory T cells exhibited reduced effector function compared to adults. Transcription factor network analysis identified HELIOS and KLF6 as regulators of memory T cell states in infant and adult tissues, respectively.
Using single-nucleus RNA sequencing, assay for transposase-accessible chromatin sequencing and CRISPR–Cas9 knockout, we defined HELIOS ( IKZF2 ) as a critical regulator of the infant-specific transcriptional program in CCL5 + effector memory T cells and restricted effector function in SELL + CCR7 + naive and/or central memory T cells. Our findings reveal key mechanisms controlling T cell functional states in early life.
Nature Immunology published a clinical update in Infectious Disease on 02 Jun 2026.
The item focuses on Distinct transcription factors control tissue adaptation and effector function in infant and adult memory T cells.
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