Restoration of thymic T-cell development by bone marrow transplantation in mouse radiation lymphomagenesis

TL;DR

Bone marrow transplants help restore T-cell development in mice exposed to radiation, preventing lymphoma.

Contribution

This study reveals how bone marrow cells interact with recipient cells to restore T-cell differentiation after radiation.

Findings

Bone marrow transplantation restores thymic T-cell differentiation in irradiated mice.

Transplanted BM cells interact with recipient cells to recover DN2 and DN3 thymocyte populations.

Restored T-cell differentiation is crucial for preventing radiation-induced thymic lymphoma.

Abstract

Fractionated total body irradiation (TBI) with X-rays induces thymic lymphoma/leukemia (TL) in C57BL/6 mice. Radiation-induced mouse TL (RITL) can be prevented by bone marrow transplantation (BMT) of unirradiated BM cells. However, the mechanisms underlying the prevention of RITL with BMT remain unclear. Here, we show that BMT restores thymic T-cell differentiation in mice subjected to TBI. TBI (four times of 1.8 Gy X-rays weekly) was conducted with C57BL/6 mice. BMT was performed immediately after the last irradiation of TBI in mice by transplantation of BM cells isolated from enhanced green fluorescence protein (eGFP) transgenic mice. Thymic cell numbers were drastically decreased in TBI and TBI + BMT mice compared to those in non-irradiated mice. Flow cytometry showed a dramatic decrease in double negative (DN, CD4−CD8−) thymocytes, especially DN2 (CD25+CD44+) and DN3 (CD25+CD44−) subpopulations, in the TBI mice on Day 10 after the last irradiation. In contrast, the DN2 and DN3 populations were recovered in TBI + BMT mice. Interestingly, these restored DN2 and DN3 cells mainly differentiated from eGFP-negative recipient cells but not from eGFP-positive donor cells, suggesting that transplanted BM cells may interact with recipient cells to restore thymic T-cell development in the RITL model. Taken together, our findings highlight the significance of restoring thymic T-cell differentiation by BMT in RITL prevention.

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