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Stromal derived factor‐1α (SDF‐1α) induces CD4 + T cell apoptosis via the functional up‐regulation of the Fas (CD95)/Fas ligand (CD95L) pathway
Author(s) -
Colamussi Maria Luisa,
Secchiero Paola,
Gonelli Arianna,
Marchisio Marco,
Zauli Giorgio,
Capitani Silvano
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.2.263
Subject(s) - jurkat cells , fas receptor , fas ligand , apoptosis , biology , stromal cell , microbiology and biotechnology , tumor necrosis factor alpha , t cell , programmed cell death , cancer research , immunology , immune system , biochemistry
Stromal‐derived factor‐1α (SDF‐1α), 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‐1α‐mediated Jurkat cell apoptosis was observed in serum‐free or serum‐containing cultures, peaked at SDF‐1α 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‐1α did not modify the expression of TNF‐α 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‐1α to induce apoptosis was inhibited by an anti‐CD95 Fab′ neutralizing antibody. These findings suggest a role for SDF‐1α in the homeostatic control of CD4 + T‐cell survival/apoptosis mediated by the CD95‐CD95L pathway.