A CASPASE INHIBITOR PROTECTS THYMOCYTES FROM DIVERSE SIGNAL-MEDIATED APOPTOSIS BUT NOT FROM CLONAL DELETION IN FETAL THYMUS ORGAN-CULTURE

A family of caspases has been implicated as an effector in various for ms of apoptosis. The present study investigated whether this family of proteases is involved in the induction of intrathymic clonal deletion in comparison with apoptosis induced in the thymus by various signals . Potent apoptosis of thymocytes was induced in fetal thymus organ cul tures (FTOC) when FTOC were treated with glucocorticoid, radiation, an d anti-CD3 monoclonal antibody (mAb). As a model of negative selection based on apoptotic clonal deletion, the elimination of V beta 8-expre ssing thymocytes was induced by inoculating Staphylococcal enterotoxin B (SEB) into FTOC. Addition of a peptide-based caspase inhibitor resu lted in the protection of thymocytes from apoptosis induced by glucoco rticoid, radiation, and anti-CD3 mAb. In contrast, the same treatment failed to prevent clonal deletion of V beta 8(high) thymocytes. These results suggest that different pathways of cell death operate in the t hymus that may be distinguished depending on the caspase/protease util ized in each pathway. (C) 1998 Published by Elsevier Science B.V. All rights reserved.