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 languageEnglish
Article number225
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2018

Cite this

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