TY - JOUR
T1 - SDF-1α degrades whereas glycoprotein 120 upregulates Bcl-2 interacting mediator of death extralong isoform
T2 - Implications for the development of T cell memory
AU - Trushin, Sergey A.
AU - Carena, Alberto A.
AU - Bren, Gary D.
AU - Rizza, Stacey A.
AU - Dong, Xiangyang
AU - Abraham, Roshini S.
AU - Badley, Andrew D.
PY - 2012/8/15
Y1 - 2012/8/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1100275
DO - 10.4049/jimmunol.1100275
M3 - Article
C2 - 22802411
AN - SCOPUS:84864819475
SN - 0022-1767
VL - 189
SP - 1835
EP - 1842
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -