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

• Published in: Nature communications Vol. 9; no. 1; pp. 225 - 15
• Main Authors: Ju, Ji-Min, Jung, Min Ho, Nam, Giri, Kim, Woojin, Oh, Sehwa, Kim, Hyun Duk, Kim, Joo Young, Chang, Jun, Lee, Sung Hak, Park, Gyeong Sin, Min, Chang-Ki, Lee, Dong-Sup, Kim, Moon Gyo, Choi, Kyungho, Choi, Eun Young
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.01.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 14/5; 631/250/1619/554/1834/1269; 631/250/1904; 64/60; Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens; Avidity; Bone marrow; Bone marrow transplantation; Bone Marrow Transplantation - methods; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Clonal deletion; Effector cells; Flow Cytometry; Hematology; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - metabolism; Humanities and Social Sciences; Leukemia; Lymphocytes; Lymphocytes T; Mice, Knockout; Mice, Transgenic; Minor histocompatibility antigens; Minor Histocompatibility Antigens - genetics; Minor Histocompatibility Antigens - immunology; Minor Histocompatibility Antigens - metabolism; multidisciplinary; Negative selection; Rodents; Science; Science (multidisciplinary); Thymocytes - immunology; Thymocytes - metabolism; Thymus; Thymus Gland - immunology; Thymus Gland - metabolism; Transplantation; Transplantation Immunology - immunology; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-02665-z

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. Antigen distribution patterns affect thymic negative selection. Here, the authors show that incomplete thymic negative selection occurs to T cells for hematopoietic cell-restricted antigen H60 in mice, driving graft-versus-leukemia after H60-mismatched bone marrow transplantation.