Bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8-T cell progenitors

Proliferative expansion and apoptotic cell death play prominent roles in T cell development. The molecular control of cell cycle progression and apoptosis appear to be inter-connected since the Bcl-2 protein can inhibit apoptosis and slow cell cycle progression in cortical thymocytes and mature T cells, particularly during the transition from the quiescent state into the cell cycle, Here the impact of bcl-2 transgene expression on CD3(-)CD4(-)CD8(-) T cell progenitors was assessed, Bcl-2 enhanced the survival of these progenitors at all of the four major differentiation stages, CD25(-)CD44(+) (pro-T1), CD25(+)CD44(+) (pro-T2), CD25(+)CD44(-)(pro-T3) and CD25(-)CD44(-)(pro-T4). However, it reduced cell cycling and slowed turnover only in the pro-T4 subset. From an analysis of bcl-2 transgenic mice expressing a TCR transgene or bearing a mutation in the scid or rag-1 gene we conclude that Bcl-2 inhibits proliferation only of T cell progenitors that are activated via the pre-TCR, not those stimulated via c-Kit and the IL-7 receptor.