BCL-X(L) AND BCL-2 REPRESS A COMMON PATHWAY OF CELL-DEATH

The effect of Bcl-x(L) upon the developmental death of T cells was assessed by generating transgenic mice that expressed Bcl-x(L) within all thymocyte subsets. Bcl-x(L) protected thymocytes from a variety of apoptotic stimuli, including gamma irradiation, glucocorticoids, and anti-CDS treatment. Bcl-x(L) altered thymocyte maturation, resulting in increased numbers of CD3(int/hi) and CD4(-)8(+) thymocytes. Overall, the phenotype of Bcl-x(L) transgenics was essentially indistinguishable from a Bcl-2 transgenic model. Overexpression of Bcl-x(L) or Bcl-2 resulted in the down-regulation of the other molecule, providing further evidence of their reciprocal regulation. In a genetic test of redundancy, the Bcl-x(L) transgene rescued mature T cells in Bcl-2 null mice. Immunoprecipitation indicated that Bcl-x(L), like Bcl-2, heterodimerized with the death-promoting molecule Bar in thymocytes. This in vivo model argues that Bcl-x(L), like Bcl-2, functions in a common pathway to repress cell death.