Escape from thymic deletion and anti-leukemic effects of T cells specific for hematopoietic cell-restricted antigen.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29335408.
- Also identified by DOI 10.1038/s41467-017-02665-z and PMC identifier 5768767.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>+</sup> 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<sup>+</sup> hematological tumors. These results provide information essential for understanding thymic negative selection and developing a strategy to treat hematological tumors.
Medical subject headings
- CD8-Positive T-Lymphocytes
- Hematopoietic Stem Cells
- Minor Histocompatibility Antigens
- Thymus Gland