SDF-1α degrades while gp120 upregulates BimEL: implications for the development of T cell memory

摘要

Following a primary immune response, T cell memory occurs when a subset of antigen specific T cells resist peripheral selection by acquiring resistance to TCR induced death. Recent data have implicated Bim as an essential mediator of the contraction phase of T cell immunity. Herein, we describe that SDF-1α ligation of CXCR4 on activated T cells, promotes two parallel processes which favor survival, phospho-inactivation of Foxo3A as well as BimEL degradation, both in an Akt and Erk dependent manner. Activated primary CD4 T cells treated with SDF-1α therefore become resistant to the pro-apoptotic 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 as it causes p38 dependent BimEL upregulation. However when activated CD4 T cells are treated with both gp120 and SDF-1α, the SDF-1α driven effects of BimEL degradation and acquired resistance to TCR induced death predominate. These results provide a novel causal link between SDF-1α induced chemotaxis, degradation of BimEL and the development of CD4 T cell memory.