Department of Charged Particle Therapy Research, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan.
J Radiat Res. 2024 Jul 22;65(4):555-560. doi: 10.1093/jrr/rrae045.
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.
分次全身照射（TBI）用 X 射线诱导 C57BL/6 小鼠发生胸腺淋巴瘤/白血病（TL）。未照射骨髓细胞的骨髓移植（BMT）可预防辐射诱导的小鼠 TL（RITL）。然而，BMT 预防 RITL 的机制尚不清楚。在这里，我们表明 BMT 可恢复 TBI 小鼠的胸腺 T 细胞分化。用 C57BL/6 小鼠进行 TBI（每周 4 次，每次 1.8 Gy X 射线）。在 TBI 最后一次照射后，立即通过移植来自增强型绿色荧光蛋白（eGFP）转基因小鼠的 BM 细胞进行 BMT。与未照射的小鼠相比，TBI 和 TBI+BMT 小鼠的胸腺细胞数量明显减少。流式细胞术显示，在最后一次照射后第 10 天，TBI 小鼠的双阴性（DN，CD4-CD8-）胸腺细胞数量急剧减少，尤其是 DN2（CD25+CD44+）和 DN3（CD25+CD44-）亚群。相比之下，DN2 和 DN3 亚群在 TBI+BMT 小鼠中得到恢复。有趣的是，这些恢复的 DN2 和 DN3 细胞主要来自于 eGFP 阴性受体细胞而不是 eGFP 阳性供体细胞分化而来，这表明移植的 BM 细胞可能与受体细胞相互作用，以恢复 RITL 模型中的胸腺 T 细胞发育。总之，我们的研究结果强调了 BMT 恢复 RITL 预防中胸腺 T 细胞分化的重要性。
