CD10 plays a specific role in early thymic development
Guérin, S.; Mari, B.; Maulon, L.; Belhacène, N.; Marguet, D.; Auberger, P.
FASEB Journal 11(5): 376-381
1997
ISSN/ISBN: 0892-6638 PMID: 9141505 Document Number: 472375
Development of T lymphocyte is a complex process that depends on both thymocyte-stromal cell interactions and the production of soluble factors such as cytokines, peptides, and hormones. In many tissues, the concentration of active biological peptides is regulated locally by a specialized family of enzymes: the ectopeptidases. We show here that treatment of fetal thymic organ cultures (FTOC) with the specific CD10 (endopeptidase 24.11) inhibitors SCH 32615: (N-(L-(1-carboxy-2-phenyl)ethyl)-L-phenylalanyl-beta-alanine), RB25: (N-(3-((hydroaxyamino)carbonyl)-2-benzylidene-1-oxopropyl)-N-glycine), and thymopentin (TP5) results in the inhibition of thymocyte differentiation. Each agent induces a significant decrease in the number of double positive (CD4+CD8+) cells in favor of the TN (TcR-alpha-beta-CD4-CD8-) population. RB25 also blocks T lymphocyte differentiation in FTOC when preinjected into pregnant mice. Finally, RB25 and TP5 were also shown to reduce the number of CD44+CD25- and CD44-CD25- thymocytes both in vitro and after preinjection in vivo in day 2 FTOC. Thus, agents that affect endopeptidase 24.11 activity impair T cell development both in vitro and in vivo. Our results show that the CD10 molecule plays a specific role in promoting early T cell development.