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(Journal of Leukocyte Biology. 2001;69:263-270.)
© 2001 by Society for Leukocyte Biology

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

Maria Luisa Colamussi^*, Paola Secchiero^*, Arianna Gonelli^*, Marco Marchisio, Giorgio Zauli and Silvano Capitani^*

^* Department of Morphology and Embriology, Human Anatomy Section, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy
Institute of Normal Morphology, "G. d’Annunzio" University of Chieti, 66100 Chieti Scalo (CH), Italy

Correspondence: Silvano Capitani, M.D., Ph.D., Department of Morphology and Embriology, Human Anatomy Section, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy. E-mail: cps{at}dns.unife.it

Stromal-derived factor-1 (SDF-1), 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-1-mediated Jurkat cell apoptosis was observed in serum-free or serum-containing cultures, peaked at SDF-1 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 did not modify the expression of TNF- 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 to induce apoptosis was inhibited by an anti-CD95 Fab' neutralizing antibody. These findings suggest a role for SDF-1 in the homeostatic control of CD4⁺ T-cell survival/apoptosis mediated by the CD95-CD95L pathway.

Key Words: T lymphocytes • CXCR4 • TNF- • TNF-RI • TNF-RII

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