A1 is a growth-permissive antiapoptotic factor mediating postactivation survival in T cells

• Published in: Blood Vol. 101; no. 7; pp. 2679 - 2685
• Main Authors: Gonzalez, Juana, Orlofsky, Amos, Prystowsky, Michael B.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.04.2003; The Americain Society of Hematology
• Subjects: Animals; Apoptosis; Biological and medical sciences; Cell Division; Cell Survival; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation; Immunobiology; Lymphocyte Activation; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Transgenic; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - physiology; Replication Protein C; RNA, Messenger - biosynthesis; Spleen - cytology; T-Lymphocytes - cytology; T-Lymphocytes - metabolism; Thymus Gland - cytology; Immune response; Rodentia; Naive cell; Vertebrata; Regulation(control); Mammalia; Mouse; Cell death; Animal; C-Onc gene; Cell cycle; T-Lymphocyte; Protooncogene; Apoptosis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-04-1229

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.