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

Juana Gonzalez, Amos Orlofsky, Michael B. Prystowsky

Research output: Contribution to journalArticle

43 Citations (Scopus)

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 Ick 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.

Original languageEnglish (US)
Pages (from-to)2679-2685
Number of pages7
JournalBlood
Volume101
Issue number7
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

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T-cells
T-Lymphocytes
Growth
Chemical activation
Cell death
Cell Death
Apoptosis
bcl-2 Genes
Aptitude
Thymocytes
Concanavalin A
T-Cell Antigen Receptor
S Phase
Cell culture
Gene expression
Genes
Gene Expression
Messenger RNA
Antibodies
Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

A1 is a growth-permissive antiapoptotic factor mediating postactivation survival in T cells. / Gonzalez, Juana; Orlofsky, Amos; Prystowsky, Michael B.

In: Blood, Vol. 101, No. 7, 01.04.2003, p. 2679-2685.

Research output: Contribution to journalArticle

Gonzalez, Juana ; Orlofsky, Amos ; Prystowsky, Michael B. / A1 is a growth-permissive antiapoptotic factor mediating postactivation survival in T cells. In: Blood. 2003 ; Vol. 101, No. 7. pp. 2679-2685.
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