Requirement for Surface Aminopeptidase Activities during Development of CD8+Fetal Thymocytes

The role of surface aminopeptidases (APs), enzymes that cleave amino-terminal residues from polypeptide chains, in the development of fetal thymocytes was studied using a murine fetal thymic organ culture (FTOC) model. FTOC AP activity was demonstrable for various amino acid–p-nitroanilide substrates, and specific inhibitors of AP (amastatin and bestatin) inhibited enzymatic activity. AP activity decreased from Day 4 to Day 7 in FTOC. Inhibition of AP activity during thymic development by FTOC in the presence of bestatin caused a significant selective decrease in the percentage of CD8+cells (both CD4+CD8+and CD4−CD8+). Bestatin did not downregulate expression of CD8 by a mature CD8+T cell clone. These data suggest that APs are involved in the development of thymocytes expressing CD8.