Flt3 ligand-receptor interaction is important for maintenance of early thymic progenitor numbers in steady-state thymopoiesis.
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.
Kenins
Linda
L
Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Gill
Jason W
JW
Holländer
Georg A
GA
Wodnar-Filipowicz
Aleksandra
A
D000818:Animals; D002454:Cell Differentiation; D005260:Female; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*; D046509:Tissue Culture Techniques; D015854:Up-Regulation; D051941:fms-Like Tyrosine Kinase 3 / Q000276:immunology*
D008565:Membrane Proteins; C084881:flt3 ligand protein; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3