Stromal derived factor-1 alpha (SDF-1 alpha) 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 C XC-chemokine receptor 4 (CXCR4), induced a progressive increase of apoptosi s when added to tbe Jurkat CD4(+)/CXCR4(+) T cell line. The SDF-1 alpha -me diated 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 T NF-alpha or that of TNF-RI and TNF-RII, it increased the expression of surf ace Fas/APO-1 (CD95) and intracellular Fas ligand (CD95L) significantly. Mo reover, 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 med iated by the CD95-CD95L pathway.