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; Eun Young Choi

doi:10.1038/s41467-017-02665-z

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, Eun Young Choi

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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.

Original language	English
Article number	225
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-02665-z
State	Published - 1 Dec 2018

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Ju, J. M., Jung, M. H., Nam, G., Kim, W., Oh, S., Kim, H. D., Kim, J. Y., Chang, J., Lee, S. H., Park, G. S., Min, C. K., Lee, D. S., Kim, M. G., Choi, K., & Choi, E. Y. (2018). Escape from thymic deletion and anti-leukemic effects of T cells specific for hematopoietic cell-restricted antigen. Nature Communications, 9(1), [225]. https://doi.org/10.1038/s41467-017-02665-z

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

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.",

author = "Ju, {Ji Min} and Jung, {Min Ho} and Giri Nam and Woojin Kim and Sehwa Oh and Kim, {Hyun Duk} and Kim, {Joo Young} and Jun Chang and Lee, {Sung Hak} and Park, {Gyeong Sin} and Min, {Chang Ki} and Lee, {Dong Sup} and Kim, {Moon Gyo} and Kyungho Choi and Choi, {Eun Young}",

note = "Funding Information: This study was supported by grants from Seoul National University Hospital, the National Research Foundation funded by the Ministry of Science and ICT (Basic Science Research Program 2016R1A2B3016080; Basic Research Laboratory 2017R1A4A1015745) and the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare (HI16C0047), Republic of Korea. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

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doi = "10.1038/s41467-017-02665-z",

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T1 - Escape from thymic deletion and anti-leukemic effects of T cells specific for hematopoietic cell-restricted antigen

AU - Ju, Ji Min

AU - Jung, Min Ho

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AU - Kim, Woojin

AU - Oh, Sehwa

AU - Kim, Hyun Duk

AU - Kim, Joo Young

AU - Chang, Jun

AU - Lee, Sung Hak

AU - Park, Gyeong Sin

AU - Min, Chang Ki

AU - Lee, Dong Sup

AU - Kim, Moon Gyo

AU - Choi, Kyungho

AU - Choi, Eun Young

N1 - Funding Information: This study was supported by grants from Seoul National University Hospital, the National Research Foundation funded by the Ministry of Science and ICT (Basic Science Research Program 2016R1A2B3016080; Basic Research Laboratory 2017R1A4A1015745) and the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare (HI16C0047), Republic of Korea. Publisher Copyright: © 2018 The Author(s).

PY - 2018/12/1

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N2 - 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.

AB - 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.

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

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