Bcl-XL displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal deletion in transgenic mice

doi:10.1084/jem.182.6.1973

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Bcl-XL displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal deletion in transgenic mice

DA Grillot, R Merino and G Nunez
Department of Pathology, University of Michigan, Ann Arbor 48109-0608, USA.

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