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J. Exp. Med.,
Volume 188, Number 6, September 21, 1998 1125-1133
By
From the Division of Molecular Immunology, Medical Research Council, National Institute for
Medical Research, London NW7 1AA, United Kingdom
T cell development and selection in the thymus are shaped by the induction of apoptosis.
However, a direct role in T cell development and selection for any of the molecules known to
regulate apoptosis has remained controversial. We have studied the effect of bax and bcl-2 transgenes in recombination activation gene 1-deficient (RAG-1
/) mice transgenic for the major
histocompatibility complex class I-restricted F5 T cell receptor. Overexpression of a bax transgene in the thymus seriously impairs the production of mature T cells, whereas bcl-2 overexpression greatly promotes it. The effect of bax and bcl-2 overexpression on antigen-induced
negative selection was studied using fetal thymic organ cultures. This analysis showed that Bcl-2
strongly inhibits negative selection, whereas Bax does not affect it. Our data directly show
that Bcl-2 family members have specific roles in T cell selection and also lend support to the
hypothesis that Bax and Bcl-2 can antagonize each other's action in a certain apoptosis pathway
while in another they can be functionally nonreciprocal.
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