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Requirement for surface aminopeptidase activities during development of CD8+ fetal thymocytes
P M Appasamy1, T W Kenniston, A A Amoscato
1University of Pittsburgh Cancer Institute and Department of Pathology, University of Pittsburgh, School of Medicine, Pennsylvania 15213, USA. gastrot@pitt.edu
Abstract:
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.