A1 is a growth-permissive antiapoptotic factor mediating postactivation survival in T cells.
The regulation of cell death in activated naive T cells is not well understood. We examined the expression of A1, an antiapoptotic member of the Bcl-2 family, following activation of naive mouse splenocytes. A1 gene expression was strongly but transiently induced during the first day of activation, with a peak at 2 to 6 hours, whereas Bcl-2 mRNA was simultaneously transiently down-regulated. Transgenic (Tg) overexpression of A1-a in T cells via the lck distal promoter resulted in decreased apoptosis following activation either with concanavalin A or with antibodies to CD3 and CD28 and led to a doubling of T-cell yield by 5 days. Tg A1-a also partially protected thymocytes from several proapoptotic stimuli but did not protect T-cell blasts from cell death induced by reactivation via the T-cell receptor. Tg Bcl-2 and Tg A1-a showed a similar ability to reduce apoptosis in both resting and activated T cells. However, in activated splenocyte cultures, the increase in 5-day T-cell yield observed with Tg Bcl-2 was only half that produced by Tg A1-a. This difference could be attributed at least in part to the fact that A1, unlike Bcl-2, did not inhibit S-phase entry of activated cells. The A1 protein may represent an adaptation of the Bcl-2 gene family to the need for survival regulation in the context of a proliferative stimulus.
Gonzalez
Juana
J
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Orlofsky
Amos
A
Prystowsky
Michael B
MB
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051818:Replication Protein C; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology
D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051818:Replication Protein C