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

Blood. 2003 Apr 1;101(7):2679-85. doi: 10.1182/blood-2002-04-1229. Epub 2002 Oct 24.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Division
  • Cell Survival
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation
  • Lymphocyte Activation*
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • RNA, Messenger / biosynthesis
  • Replication Protein C
  • Spleen / cytology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Replication Protein C