Regulation of Thymic Development by Neprilysin Inhibition
Development of T lymphocyte is regulated by both thymocyte-stromal cell interactions and production of soluble factors such as cytokines, peptides and hormones. The local concentration of active biological peptides is regulated by a specialized family of enzymes expressed at the cell surface, the ectopeptidases. We found that treatment of fetal thymic organ cultures (FTOC) with the specific CD10 (endopeptidase 24.11) inhibitor, (N-(3-[(hydroaxyamino)carbonyl]-2-benzylidene-1-oxopropyl]-N-glycine), RB25 results in a marked delay in thymocyte differentiation. RB25 causes a significant decrease in the number of DP (CD4+CD8+) cells in favor of the TN (TcRαβ−CD4−CD8−) population. RB25 also blocks T lymphocyte differentiation in FTOC when preinjected into pregnant mice. Finally, RB25 was found to essentially affect the CD44+CD25− and CD44−CD25− thymocytes in “in vitro” and “in vivo” experiments after 2 days FTOC. Thus, a selective and stable endopeptidase 24.11 inhibitor impairs T cell development, an observation in agreement with the involvement of the CD10 antigen in early T cell development.
KeywordsPregnant Mouse Thymic Epithelial Cell Lymphocyte Differentiation Cell Surface Staining Thymic Development
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