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

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 and Eun Young Choi ()
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Ji-Min Ju: Seoul National University College of Medicine
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

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02665-z

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