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-1alpha (SDF-1alpha), the high-affinity ligand of CXC-chemokine receptor 4 (CXCR4), induced a progressive increase of apoptosis when added to the Jurkat CD4+/CXCR4+ T cell line. The SDF-1alpha-mediated Jurkat cell apoptosis was observed in serum-free or serum-containing cultures, peaked at SDF-1alpha 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-1alpha 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-1alpha to induce apoptosis was inhibited by an anti-CD95 Fab' neutralizing antibody. These findings suggest a role for SDF-1alpha in the homeostatic control of CD4+ T-cell survival/apoptosis mediated by the CD95-CD95L pathway.
Department of Morphology and Embryology, University of Ferrara, Italy.
M L
ML
Colamussi
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P
Secchiero
A
A
Gonelli
M
M
Marchisio
G
G
Zauli
S
S
Capitani
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D019138:Antibodies, Blocking / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D061945:Caspase Inhibitors; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology*; D019014:fas Receptor / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology
D000590:Amino Acid Chloromethyl Ketones; D019138:Antibodies, Blocking; C515255:CXCL12 protein, human; D061945:Caspase Inhibitors; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015853:Cysteine Proteinase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007106:Immune Sera; D008024:Ligands; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor