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Escape from thymic deletion and anti-leukemic effects of T cells specific for hematopoietic cell-restricted antigen

Author

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  • Ji-Min Ju

    (Seoul National University College of Medicine
    Division of Convergence Technology, National Cancer Center)

  • Min Ho Jung

    (Seoul National University College of Medicine)

  • Giri Nam

    (Seoul National University College of Medicine)

  • Woojin Kim

    (Seoul National University College of Medicine)

  • Sehwa Oh

    (Seoul National University)

  • Hyun Duk Kim

    (Seoul National University College of Medicine)

  • Joo Young Kim

    (Ewha Womans University)

  • Jun Chang

    (Ewha Womans University)

  • Sung Hak Lee

    (The Catholic University of Korea)

  • Gyeong Sin Park

    (The Catholic University of Korea)

  • Chang-Ki Min

    (The Catholic University of Korea)

  • Dong-Sup Lee

    (Seoul National University College of Medicine)

  • Moon Gyo Kim

    (Inha University)

  • Kyungho Choi

    (Seoul National University College of Medicine)

  • Eun Young Choi

    (Seoul National University College of Medicine
    Seoul National University)

Abstract

Whether hematopoietic cell-restricted distribution of antigens affects the degree of thymic negative selection has not been investigated in detail. Here, we show that T cells specific for hematopoietic cell-restricted antigens (HRA) are not completely deleted in the thymus, using the mouse minor histocompatibility antigen H60, the expression of which is restricted to hematopoietic cells. As a result, low avidity T cells escape from thymic deletion. This incomplete thymic deletion occurs to the T cells developing de novo in the thymus of H60-positive recipients in H60-mismatched bone marrow transplantation (BMT). H60-specific thymic deletion escapee CD8+ T cells exhibit effector differentiation potentials in the periphery and contribute to graft-versus-leukemia effects in the recipients of H60-mismatched BMT, regressing H60+ hematological tumors. These results provide information essential for understanding thymic negative selection and developing a strategy to treat hematological tumors.

Suggested Citation

  • Ji-Min Ju & Min Ho Jung & Giri Nam & Woojin Kim & Sehwa Oh & Hyun Duk Kim & Joo Young Kim & Jun Chang & Sung Hak Lee & Gyeong Sin Park & Chang-Ki Min & Dong-Sup Lee & Moon Gyo Kim & Kyungho Choi & Eun, 2018. "Escape from thymic deletion and anti-leukemic effects of T cells specific for hematopoietic cell-restricted antigen," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02665-z
    DOI: 10.1038/s41467-017-02665-z
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