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 Tcell development. The molecular control of cell cycle progression andapoptosis appear to be inter-connected since the Bcl-2 protein can inhibitapoptosis and slow cell cycle progression in cortical thymocytes and matureT cells, particularly during the transition from the quiescent state intothe cell cycle. Here the impact of bcl-2 transgene expression onCD3-CD4-CD8- T cell progenitors was assessed. Bcl-2 enhanced the survivalof these progenitors at all of the four major differentiation stages, CD25-CD44+ (pro-T1), CD25 + CD44+ (pro- T2), CD25 + CD44- (pro-T3) andCD25-CD44- (pro-T4). However, it reduced cell cycling and slowed turnoveronly in the pro-T4 subset. From an analysis of bcl-2 transgenic miceexpressing a TCR transgene or bearing a mutation in the scid or rag-1 genewe conclude that Bcl-2 inhibits proliferation only of T cell progenitorsthat are activated via the pre- TCR, not those stimulated via c-Kit and theIL-7 receptor.