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Developmental self-reactivity determines pathogenic Tc17 differentiation potential of naive CD8+ T cells in murine models of inflammation

Author

Listed:
  • Gil-Woo Lee

    (Chonnam National University Medical School
    Chonnam National University Medical School
    Chonnam National University Medical School)

  • Young Ju Kim

    (Chonnam National University Medical School
    Chonnam National University Medical School
    Chonnam National University Medical School
    Chonnam National University Medical School)

  • Sung-Woo Lee

    (Chonnam National University Medical School
    Chonnam National University Medical School
    Chonnam National University Medical School)

  • Hee-Ok Kim

    (Selecxine)

  • Daeun Kim

    (Selecxine)

  • Jiyoung Kim

    (Korea Advanced Institute of Science and Technology)

  • You-Me Kim

    (Korea Advanced Institute of Science and Technology)

  • Keunsoo Kang

    (Dankook University)

  • Joon Haeng Rhee

    (Chonnam National University Medical School
    Chonnam National University Medical School
    Chonnam National University Medical School)

  • Ik Joo Chung

    (Chonnam National University Medical School
    Chonnam National University Medical School)

  • Woo Kyun Bae

    (Chonnam National University Medical School
    Chonnam National University Medical School)

  • In-Jae Oh

    (Chonnam National University Medical School)

  • Deok Hwan Yang

    (Chonnam National University Medical School)

  • Jae-Ho Cho

    (Chonnam National University Medical School
    Chonnam National University Medical School
    Chonnam National University Medical School
    Chonnam National University Medical School)

Abstract

The differentiation of naive CD8+ T cells into effector cells is important for establishing immunity. However, the effect of heterogeneous naive CD8+ T cell populations is not fully understood. Here, we demonstrate that steady-state naive CD8+ T cells are composed of functionally heterogeneous subpopulations that differ in their ability to differentiate into type 17 cytotoxic effector cells (Tc17) in a context of murine inflammatory disease models, such as inflammatory bowel disease and graft-versus-host disease. The differential ability of Tc17 differentiation is not related to T-cell receptor (TCR) diversity and antigen specificity but is inversely correlated with self-reactivity acquired during development. Mechanistically, this phenomenon is linked to differential levels of intrinsic TCR sensitivity and basal Suppressor of Mothers Against Decapentaplegic 3 (SMAD3) expression, generating a wide spectrum of Tc17 differentiation potential within naive CD8+ T cell populations. These findings suggest that developmental self-reactivity can determine the fate of naive CD8+ T cells to generate functionally distinct effector populations and achieve immense diversity and complexity in antigen-specific T-cell immune responses.

Suggested Citation

  • Gil-Woo Lee & Young Ju Kim & Sung-Woo Lee & Hee-Ok Kim & Daeun Kim & Jiyoung Kim & You-Me Kim & Keunsoo Kang & Joon Haeng Rhee & Ik Joo Chung & Woo Kyun Bae & In-Jae Oh & Deok Hwan Yang & Jae-Ho Cho, 2024. "Developmental self-reactivity determines pathogenic Tc17 differentiation potential of naive CD8+ T cells in murine models of inflammation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47144-4
    DOI: 10.1038/s41467-024-47144-4
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    References listed on IDEAS

    as
    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. Peng Li & Rosanne Spolski & Wei Liao & Lu Wang & Theresa L. Murphy & Kenneth M. Murphy & Warren J. Leonard, 2012. "BATF–JUN is critical for IRF4-mediated transcription in T cells," Nature, Nature, vol. 490(7421), pages 543-546, October.
    3. Jae-Ho Cho & Hee-Ok Kim & Young-Jun Ju & Yoon-Chul Kye & Gil-Woo Lee & Sung-Woo Lee & Cheol-Heui Yun & Nunzio Bottini & Kylie Webster & Christopher C. Goodnow & Charles D. Surh & Cecile King & Jonatha, 2016. "CD45-mediated control of TCR tuning in naïve and memory CD8+ T cells," Nature Communications, Nature, vol. 7(1), pages 1-15, December.
    4. Jason T. White & Eric W. Cross & Matthew A. Burchill & Thomas Danhorn & Martin D. McCarter & Hugo R. Rosen & Brian O’Connor & Ross M. Kedl, 2016. "Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner," Nature Communications, Nature, vol. 7(1), pages 1-13, September.
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