BCL-X(L) DISPLAYS RESTRICTED DISTRIBUTION DURING T-CELL DEVELOPMENT AND INHIBITS MULTIPLE FORMS OF APOPTOSIS BUT NOT CLONAL DELETION IN TRANSGENIC MICE

The survival of T lymphocytes is tightly controlled during development . Here, we show that Bcl-x(L), a protein homologue of Bcl-2, is highly regulated in the thymus in a pattern different than that of Bcl-2. Th e maximum expression was in CD4(+)CD8(+) thymocytes, a developmental s tage where Bcl-2 is downregulated. To assess the role of Bcl-x(L) in t hymocyte apoptosis, we generated mice overexpressing an E mu-bcl-x tra nsgene within the T cell compartment. Constitutive expression of Bcl-x (L) resulted in accumulation of thymocytes and mature T cells in lymph oid organs. Thymocytes overexpressing Bcl-x(L) exhibited increased via bility in vitro and were resistant to apoptosis induced by different s ignals, including glucocorticoid, gamma irradiation, calcium ionophore , and CD3 cross-linking. However, Bcl-x(L) was unable to block clonal deletion of thymocytes reactive with self-superantigens or H-Y antigen . These studies demonstrate that Bcl-2 and Bcl-x(L), two functionally related proteins, are regulated independently during T cell developmen t. In contrast to Bcl-2, which has been implicated in the maintenance of mature T cells, Bcl-x(L) appears to provide a survival signal for t he maintenance of more immature CD4(+)CD8(+) thymocytes before positiv e selection.