SDF-1α degrades whereas glycoprotein 120 upregulates Bcl-2 interacting mediator of death extralong isoform: implications for the development of T cell memory.
J Immunol
; 189(4): 1835-42, 2012 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-22802411
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(EL) upregulation. However, when activated CD4 T cells are treated with both gp120 and SDF-1α, the SDF-1α-driven effects of Bim(EL) degradation 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Proteínas Proto-Oncogênicas
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Proteínas Reguladoras de Apoptose
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Quimiocina CXCL12
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Memória Imunológica
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Proteínas de Membrana
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article