SDF-1α degrades whereas glycoprotein 120 upregulates Bcl-2 interacting mediator of death extralong isoform: Implications for the development of T cell memory

Sergey A. Trushin, Alberto A. Carena, Gary D. Bren, Stacey A. Rizza, Xiangyang Dong, Roshini S. Abraham, Andrew D. Badley

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

After a primary immune response, T cell memory occurs when a subset of Ag-specific T cells resists peripheral selection by acquiring resistance to TCR-induced death. Recent data have implicated Bcl-2 interacting mediator of death (Bim) as an essential mediator of the contraction phase of T cell immunity. In this article, we describe that stromal-derived factor-1α (SDF-1α) ligation of CXCR4 on activated T cells promotes two parallel processes that favor survival, phospho-inactivation of Foxo3A, as well as Bim extralong isoform (Bim EL) degradation, both in an Akt- and Erk-dependent manner. Activated primary CD4 T cells treated with SDF-1α therefore become resistant to the proapoptotic effects of TCR ligation or IL-2 deprivation and accumulate cells of a memory phenotype. Unlike SDF-1α, gp120 ligation of CXCR4 has the opposite effect because it causes p38-dependent Bim ELupregulation. However, when activated CD4 T cells are treated with both gp120 and SDF-1α, the SDF-1α-driven effects of Bim ELdegradation and acquired resistance to TCR-induced death predominate. These results provide a novel causal link between SDF-1α-induced chemotaxis, degradation of Bim EL, and the development of CD4 T cell memory.

Original languageEnglish (US)
Pages (from-to)1835-1842
Number of pages8
JournalJournal of Immunology
Volume189
Issue number4
DOIs
StatePublished - Aug 15 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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