期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 40, 期 1, 页码 81-90出版社
WILEY
DOI: 10.1002/eji.200839213
关键词
Early thymic progenitor; Flt3 ligand; Thymopoiesis
类别
资金
- Swiss National Science Foundation [3100-110511, 3100-68310.02]
- European Community
- NIH [ROI-A1057477-01]
T-cell production throughout life depends on efficient colonization and intrathymic expansion of BM-derived hematopoietic precursors. After irradiation-induced thymic damage, thymic recovery is facilitated by Flt3 ligand (FL), expressed by perivascular fibroblasts surrounding the thymic entry site of Flt3 receptor-positive progenitor cells. Whether intrathymic FL-Flt3 interactions play a role in steady-state replenishment of T cells remains unknown. Here, using competitive BM transplantation studies and fetal thymic organ cultures we demonstrated the continued numerical advantage of Flt3(+) intrathymic T-cell precursors. Sub-kidney capsule thymic transplantation experiments, in which WT and FL-/- thymic lobes were grafted into FL-/- recipients, revealed that FL expression by the thymic microenvironment plays a role in steady-state thymopoiesis. The deficiency of the most immature thymic T-cell precursors correlated to upregulation of FL by thymic MTS15(+) fibroblasts, suggesting that the number of Flt3(+) progenitor cells may regulate the thymic expression of this cytokine. Together, these results show that FL expression by thymic stromal fibroblasts interacting with Flt3(+) T-cell progenitors is important for the physiological maintenance of early T-cell development.
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