CD10 plays a specific role in early thymic development.
Development of T lymphocyte is a complex process that depends on both thymocytestromal 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-glyci ne), 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.
Guérin
S
S
CJF INSERM 96.05, Activation des Cellules Hematopoietique, Faculté de Médecine, Nice, France.
Mari
B
B
Maulon
L
L
Belhacène
N
N
Marguet
D
D
Auberger
P
P
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D018960:Hyaluronan Receptors / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009924:Organ Culture Techniques; D010455:Peptides / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000196:embryology*
D016827:CD8 Antigens; D018960:Hyaluronan Receptors; D010455:Peptides; D011480:Protease Inhibitors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D015260:Neprilysin