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.
O'Reilly
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Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Harris
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Strasser
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D000818:Animals; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D019254:Genes, bcl-2 / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D019076:Transgenes / Q000276:immunology*
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta