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

JM Ju, MH Jung, G Nam, W Kim, S Oh, HD Kim… - Nature …, 2018 - nature.com
JM Ju, MH Jung, G Nam, W Kim, S Oh, HD Kim, JY Kim, J Chang, SH Lee, GS Park, CK Min…
Nature Communications, 2018nature.com
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 …
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.
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