Flt3 ligand-receptor interaction is important for maintenance of early thymic progenitor numbers in steady-state thymopoiesis.

Journal article

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.

Authors: Kenins, L; Gill, J; Holländer, G; Wodnar-Filipowicz, A

• Publication status: Published
• Journal: European journal of immunology
• Volume: 40
• Issue: 1
• Pages: 81-90
• Publication date: 2010-01-01
• DOI: 10.1002/eji.200839213
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Male; Up-Regulation; Thymus Gland; Animals; Cell Differentiation; Mice; Membrane Proteins; Mice, Inbred C57BL; fms-Like Tyrosine Kinase 3; Tissue Culture Techniques; Female; Precursor Cells, T-Lymphoid