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Peer-reviewedCC BY-NC-NDNature Immunology

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

  • Peter Anthony Szabo1
  • Hanna Mendes Levitin2
  • Siddhi Nargund2
  • Thomas J. Connors3
  • David Chen2
  • Jenny Jin4
  • Puspa Thapa1
  • Rebecca S. Guyer1
  • Daniel P. Caron1
  • Joshua I. Gray1
  • Rei Matsumoto5
  • Masaru Kubota5
4 more authors
  • Maigan Brusko6
  • Todd M. Brusko6
  • Donna L. Färber7,8
  • Peter A. Sims9,10
10 affiliations
  1. 1Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA
  2. 2Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA
  3. 3Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA
  4. 4Medical Scientist Training Program, Columbia University Irving Medical Center, New York, NY, USA
  5. 5Department of Surgery, Columbia University Irving Medical Center, New York, NY, USA
  6. 6Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA
  7. 7Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA. [email protected]
  8. 8Department of Surgery, Columbia University Irving Medical Center, New York, NY, USA. [email protected]
  9. 9Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, USA. [email protected]
  10. 10Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA. [email protected]
Open at sourceDOICite

Abstract

The first years of life are essential for the development of memory T cells, which rapidly populate the body’s diverse tissue sites during infancy. However, the degree to which tissue memory T cell responses in early life reflect those during adulthood is unclear. Here, we use single cell RNA-sequencing of resting and ex vivo activated T cells from lymphoid and mucosal tissues of infant (aged 2-9 months) and adult (aged 40-65 years) human organ donors to dissect the transcriptional programming of memory T cells over age. Infant memory T cells demonstrate a unique stem-like transcriptional profile and tissue adaptation program, yet exhibit reduced activation capacity and effector function relative to adults. Using CRISPR-Cas9 knockdown, we define Helios ( IKZF2 ) as a critical transcriptional regulator of the infant-specific tissue adaptation program and restricted effector state. Our findings reveal key transcriptional mechanisms that control tissue T cell fate and function in early life.

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Cite

BibTeXRIS
BibTeX
@article{szabo2026distinct,
  title = {{Distinct transcription factors control tissue adaptation and effector function in infant and adult memory T cells}},
  author = {Peter Anthony Szabo and Hanna Mendes Levitin and Siddhi Nargund and Thomas J. Connors and David Chen and Jenny Jin and Puspa Thapa and Rebecca S. Guyer and Daniel P. Caron and Joshua I. Gray and Rei Matsumoto and Masaru Kubota and Maigan Brusko and Todd M. Brusko and Donna L. Färber and Peter A. Sims},
  journal = {Nature Immunology},
  year = {2026},
  month = jun,
  doi = {10.1038/s41590-026-02535-1},
  url = {https://doi.org/10.1038/s41590-026-02535-1},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Distinct transcription factors control tissue adaptation and effector function in infant and adult memory T cells
AU  - Peter Anthony Szabo
AU  - Hanna Mendes Levitin
AU  - Siddhi Nargund
AU  - Thomas J. Connors
AU  - David Chen
AU  - Jenny Jin
AU  - Puspa Thapa
AU  - Rebecca S. Guyer
AU  - Daniel P. Caron
AU  - Joshua I. Gray
AU  - Rei Matsumoto
AU  - Masaru Kubota
AU  - Maigan Brusko
AU  - Todd M. Brusko
AU  - Donna L. Färber
AU  - Peter A. Sims
PY  - 2026
DA  - 2026/06/02
JO  - Nature Immunology
DO  - 10.1038/s41590-026-02535-1
UR  - https://doi.org/10.1038/s41590-026-02535-1
AB  - The first years of life are essential for the development of memory T cells, which rapidly populate the body’s diverse tissue sites during infancy. However, the degree to which tissue memory T cell responses in early life reflect those during adulthood is unclear. Here, we use single cell RNA-sequencing of resting and ex vivo activated T cells from lymphoid and mucosal tissues of infant (aged 2-9 months) and adult (aged 40-65 years) human organ donors to dissect the transcriptional programming of memory T cells over age. Infant memory T cells demonstrate a unique stem-like transcriptional profile and tissue adaptation program, yet exhibit reduced activation capacity and effector function relative to adults. Using CRISPR-Cas9 knockdown, we define Helios ( IKZF2 ) as a critical transcriptional regulator of the infant-specific tissue adaptation program and restricted effector state. Our findings reveal key transcriptional mechanisms that control tissue T cell fate and function in early life.
SN  - 1529-2908
SN  - 1529-2916
ER  -