Wils Evert-Jan, Braakman Eric, Verjans Georges M G M, Rombouts Elwin J C, Broers Annoek E C, Niesters Hubert G M, Wagemaker Gerard, Staal Frank J T, Löwenberg Bob, Spits Hergen, Cornelissen Jan J
Department of Hematology, Erasmus Medical Center/Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3071 EA Amsterdam, the Netherlands.
J Immunol. 2007 Mar 15;178(6):3551-7. doi: 10.4049/jimmunol.178.6.3551.
Deficient thymopoiesis and retarded recovery of newly developed CD4(+) T cells is one of the most important determinants of impaired immunocompetence after hemopoietic stem cell transplantation. Here we evaluated whether Fms-like tyrosine kinase 3 (Flt3) ligand (FL) alone or combined with IL-7 affects T cell recovery, thymopoiesis, and lymphoid progenitor expansion following bone marrow transplantation in immunodeficient mice. FL strongly accelerated and enhanced the recovery of peripheral T cells after transplantation of a low number of bone marrow cells. An additive effect on T cell recovery was not observed after coadministration of IL-7. Lineage(-)sca-1(+)c-kit(+)flt3(+) lymphoid progenitor cell numbers were significantly increased in bone marrow of FL-treated mice before recovery of thymopoiesis. Thymocyte differentiation was advanced to more mature stages after FL treatment. Improved T cell recovery resulted in better immunocompetence against a post-bone marrow transplantation murine CMV infection. Collectively, our data suggest that FL promotes T cell recovery by enhanced thymopoiesis and by expansion of lymphoid progenitors.
胸腺生成缺陷以及新发育的CD4(+) T细胞恢复延迟是造血干细胞移植后免疫能力受损的最重要决定因素之一。在此，我们评估了Fms样酪氨酸激酶3（Flt3）配体（FL）单独使用或与IL-7联合使用是否会影响免疫缺陷小鼠骨髓移植后的T细胞恢复、胸腺生成以及淋巴祖细胞扩增。在移植少量骨髓细胞后，FL强烈加速并增强了外周T细胞的恢复。同时给予IL-7后，未观察到对T细胞恢复的相加作用。在胸腺生成恢复之前，FL处理小鼠的骨髓中谱系（-）sca-1（+）c-kit（+）flt3（+）淋巴祖细胞数量显著增加。FL处理后，胸腺细胞分化进展到更成熟阶段。改善的T细胞恢复导致对骨髓移植后小鼠巨细胞病毒感染的免疫能力增强。总体而言，我们的数据表明，FL通过增强胸腺生成和淋巴祖细胞扩增来促进T细胞恢复。
