Stromal derived factor-1α (SDF-1α) induces CD4+ T cell apoptosis via the functional up-regulation of the Fas (CD95)/Fas ligand (CD95L) pathway

Stromal-derived factor-1 alpha (SDF-1 alpha), the high-affinity ligand of CXC-chemokine receptor 4 (CXCR4), induced a progressive increase of apoptosis when added to tbe Jurkat CD4(+)/CXCR4(+) T cell line. The SDF-1 alpha -mediated Jurkat cell apoptosis was observed in serum-free or serum-containing cultures, peaked at SDF-1 alpha concentrations of 10-100 ng/ml, required 3 days to take place, and was completely blocked by the z-VAD-fmk tripeptide caspase inhibitor. Although SDF-1 alpha did not modify the expression of TNF-alpha or that of TNF-RI and TNF-RII, it increased the expression of surface Fas/APO-1 (CD95) and intracellular Fas ligand (CD95L) significantly. Moreover, the ability of SDF-1 alpha to induce apoptosis was inhibited by an anti-CD95 Fab' neutralizing antibody. These findings suggest a role for SDF-1 alpha in the homeostatic control of CD4(+) T-cell survival/apoptosis mediated by the CD95-CD95L pathway.