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Th1-poised naive CD4 T cell subpopulation reflects anti-tumor immunity and autoimmune disease

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Listed:
  • Jae-Won Yoon

    (Hanyang University)

  • Kyung Min Kim

    (Seoul National University)

  • Sookyung Cho

    (Hanyang University)

  • Min-Ji Cho

    (Hanyang University)

  • Seonjun Park

    (Ulsan National Institute of Science & Technology (UNIST))

  • Daehee Hwang

    (Seoul National University)

  • Hye Ryun Kim

    (Yonsei Cancer Center Yonsei University College of Medicine)

  • Sung Ho Park

    (Ulsan National Institute of Science & Technology (UNIST))

  • Jae-Ho Cho

    (Chonnam National University Medical School)

  • Hyobin Jeong

    (Yonsei University)

  • Je-Min Choi

    (Hanyang University
    Hanyang University
    Hanyang University
    Hanyang University)

Abstract

Naïve CD4 T cells are traditionally viewed as a quiescent, homogeneous, resting population, but emerging evidence reveals their heterogeneity, which can be crucial for understanding disease contexts and therapeutic outcomes. In this study, we identify distinct subpopulations within both murine and human naïve CD4 T cells by single cell-RNA-sequencing (scRNA-seq), particularly focusing on a subpopulation that expresses super-high levels of interleukin-7 receptor (IL-7Rsup-hi), along with CD97, IL-18R, and Ly6C. This subpopulation, absent in the thymus and peripherally induced, exhibits type 1 helper T cell (Th1)-poised characteristics and contributes to the inhibition of cancer progression in B16F10 tumor-bearing mice. In humans, this IL-7Rsup-hi subpopulation expressing CD97 correlates with the responsiveness to anti-PD-1 therapy in cancer patients and the disease state of multiple sclerosis. By elucidating the heterogeneity of naive CD4 T cells and identifying a Th1-poised subpopulation capable of robust type 1 responses, we highlight the importance of this heterogeneity in inflammatory conditions for defining the disease states and predicting drug responsiveness.

Suggested Citation

  • Jae-Won Yoon & Kyung Min Kim & Sookyung Cho & Min-Ji Cho & Seonjun Park & Daehee Hwang & Hye Ryun Kim & Sung Ho Park & Jae-Ho Cho & Hyobin Jeong & Je-Min Choi, 2025. "Th1-poised naive CD4 T cell subpopulation reflects anti-tumor immunity and autoimmune disease," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57237-3
    DOI: 10.1038/s41467-025-57237-3
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    References listed on IDEAS

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    1. Young-Jun Ju & Sung-Woo Lee & Yoon-Chul Kye & Gil-Woo Lee & Hee-Ok Kim & Cheol-Heui Yun & Jae-Ho Cho, 2021. "Self-reactivity controls functional diversity of naive CD8+ T cells by co-opting tonic type I interferon," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Takeshi Kawabe & Jaeu Yi & Akihisa Kawajiri & Kerry Hilligan & Difeng Fang & Naoto Ishii & Hidehiro Yamane & Jinfang Zhu & Dragana Jankovic & Kwang Soon Kim & Giorgio Trinchieri & Alan Sher, 2020. "Requirements for the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes under steady state," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    3. Bruno Martin & Cédric Auffray & Arnaud Delpoux & Arnaud Pommier & Aurélie Durand & Céline Charvet & Philippe Yakonowsky & Hubert de Boysson & Nelly Bonilla & Alexandra Audemard & Tim Sparwasser & Beno, 2013. "Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells," Nature Communications, Nature, vol. 4(1), pages 1-12, October.
    4. Hong-Gyun Lee & Jae-Ung Lee & Do-Hyun Kim & Sangho Lim & Insoo Kang & Je-Min Choi, 2019. "Pathogenic function of bystander-activated memory-like CD4+ T cells in autoimmune encephalomyelitis," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
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