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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-04-1229.
Submitted April 24, 2002
Accepted September 22, 2002
A1 is a growth-permissive anti-apoptotic factor mediating post-activation survival in T cells
Juana Gonzalez, Amos Orlofsky*, and Michael B Prystowsky
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
* Corresponding author; email: orlofsky{at}aecom.yu.edu.
The regulation of cell death in activated naive T cells is not well understood. We examined the expression of A1, an anti-apoptotic 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, while Bcl-2 mRNA was simultaneously transiently downregulated. Transgenic (Tg) overexpression of A1-a in T cells via the lck distal promoter resulted in decreased apoptosis following activation with either Con A or anti-CD3 + anti-CD28 and led to a doubling of T cell yield by 5d. Tg A1-a also partially protected thymocytes from several pro-apoptotic stimuli but did not protect T cell blasts from cell death induced by re-activation via the TCR. Tg Bcl-2 and Tg A1-a showed 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.
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