CD10 PLAYS A SPECIFIC ROLE IN EARLY THYMIC DEVELOPMENT

Development of T lymphocyte is a complex process that depends on both thymocyte-stromal cell interactions and the production of soluble fact ors such as cytokines, peptides, and hormones. In many tissues, the co ncentration of active biological peptides is regulated locally by a sp ecialized family of enzymes: the ectopeptidases. We show here that tre atment of fetal thymic organ cultures (FTOC) with the specific CD10 (e ndopeptidase 24.11)inhibitors SCH 32615: boxy-2-phenyl)ethyl]-L-phenyl alanyl-beta-alanine), RB25: o)carbonyl]-2-benzylidene-1-oxopropyl]-N-g lycine), and thymopentin (TP5) results in the inhibition of thymocyte differentiation. Each agent induces a significant decrease in the numb er of double positive (CD4(+) CD8(+)) cells in favor of the TN (TcR al pha beta(-)CD4(-)Cd8(-)) population. RB25 also blocks T lymphocyte dif ferentiation in FTOC when preinjected into pregnant mice. Finally, RB2 5 and TP5 were also shown to reduce the number of CD44(+)CD25(-) and C D44(-)CD25(-) thymocytes both in vitro and after preinjection in vivo in day 2 FTOC. Thus, agents that affect endopeptidase 24.11 activity i mpair T cell development both in vitro and in vivo. Our results show t hat the CD10 molecule plays a specific role in promoting early T cell development.