Cell
Volume 67, Issue 5, 29 November 1991, Pages 879-888
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Article
bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes

https://doi.org/10.1016/0092-8674(91)90361-2Get rights and content

Abstract

The vast majority of cortical thymocytes die during T cell development while those that survive this selective process accumulate in the medulla. bcl-2, an inner mitochondrial membrane protein, has been shown to inhibit apoptosis in certain cell lines. In the thymus, bcl-2 is regionally localized to the mature T cells of the medulla. To assess the role of bcl-2 in the programmed death of thmocytes, we generated transgenic mice that redirected bcl-2 expression to cortical thymocytes. bcl-2 protected immature CD4+8+ thymocytes from glucocorticoid, radiation, and anti-CD3-induced apoptosis. Moreover, bcl-2 altered T cell maturation, resulting in increased percentages of CD3hi and CD48+ thymocytes. Despite this, clonal deletion of T cells that recognize endogenous superantigens still occurred. This transgenic model indicates that multiple death pathways operate within the thymus that can be distinguished by their dependence on bcl-2.

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