Elevated Bcl-2 is not a causal event in the positive selection of T cells

T cell development is characterized by the induction of apoptosis in most i mmature thymocytes and the rescue from apoptosis of a small proportion of c ells by the process of positive selection. Up-regulation of the anti-apopto tic molecule Bcl-2 is associated with thymocytes undergoing positive select ion and a bcl-2 transgene promotes the generation of mature T cells. In con trast, mice transgenic for the pro-apoptotic molecule Bax show impaired T c ell maturation. We have used fetal thymic organ culture to determine the ac tion of Bcl-2 and Bax on positive selection of thymocytes. Our data show th at Bcl-2 and Bax do not alter the number of thymocytes positively selected by a defined peptide ligand. This implies that Bcl-2 and Bax alter the prod uction of mature T cells in vivo by influencing thymocyte viability rather than by direct action on positive selection. It also presents a solution to the 'chicken-and-egg' scenario relating to Bcl-2 up-regulation and positiv e selection. The data suggest that the up-regulation of Bcl-2 associated wi th T cell maturation is a consequence of positive selection rather than a c ause of it.