bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes

CL Sentman, JR Shutter, D Hockenbery, O Kanagawa… - Cell, 1991 - cell.com
CL Sentman, JR Shutter, D Hockenbery, O Kanagawa, SJ Korsmeyer
Cell, 1991cell.com
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,
sbcl-2 is regionally localized to the mature T cells of the medulla. To assess the role of bcl-2
in the programmed death of thymocytes, we generated transgenic mice 'that redirected bcl-2
expression to cortical thymocytes. bcl-2 protected immature CD4+ 8+ thymocytes from …
Summary
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, sbcl-2 is regionally localized to the mature T cells of the medulla. To assess the role of bcl-2 in the programmed death of thymocytes, 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 CD4-8+‘thymocytes. Despite this, clonal deletion of T cells that, recognize endogenous superantigens still occurred. This transgenic model indicates that multi, ple death pathways operate within the thymus that can be distinguished by their dependence on bcl-2.
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