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<p>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 <i>CCL5</i><sup><i>+</i></sup> 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 (<i>IKZF2</i>) as a critical regulator of the infant-specific transcriptional program in <i>CCL5</i><sup><i>+</i></sup> effector memory T cells and restricted effector function in <i>SELL</i><sup><i>+</i></sup><i>CCR7</i><sup><i>+</i></sup> naive and/or central memory T cells. Our findings reveal key mechanisms controlling T cell functional states in early life.</p>

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Distinct transcription factors control tissue adaptation and effector function in infant and adult memory T cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月2日

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  • Peter A. Szabo,
  • Hanna M. Levitin,
  • Siddhi Nargund,
  • Thomas J. Connors,
  • David Chen,
  • Jenny Jin,
  • Puspa Thapa,
  • Rebecca Guyer,
  • Daniel P. Caron,
  • Joshua I. Gray,
  • Rei Matsumoto,
  • Masaru Kubota,
  • Maigan Brusko,
  • Todd M. Brusko,
  • Donna L. Farber,
  • Peter A. Sims

摘要

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.