THE ACTION OF BAX AND BCL-2 ON T-CELL SELECTION

T cell development and selection in the thymus are shaped by the induc tion of apoptosis. However, a direct role in T cell development and se lection for any of the molecules known to regulate apoptosis has remai ned controversial. We have studied the effect of bar and bcl-2 transge nes in recombination activation gene l-deficient (RAG-1(-/-)) mice tra nsgenic for the major histocompatibility complex class I-restricted F5 T cell receptor. Overexpression of a box transgene in the thymus seri ously impairs the production of mature T cells, whereas bcl-2 overexpr ession greatly promotes it. The effect of box and bcl-2 overexpression on antigen-induced negative selection was studied using fetal thymic organ cultures. This analysis showed that Bcl-2 strongly inhibits nega tive selection, whereas Bar 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 Bar and Bcl-2 can antagonize each other's action in a certain apoptosis pathway while in another t hey can be functionally nonreciprocal.