title: The C-class chemokine lymphotactin costimulates the apoptosis of human CD4(+) T cells.
abstract: Clonal expansion of activated T cells is controlled by homeostatic mechanisms leading to cell death of a large proportion of the cells. The CD3/TcR pathway induces cell death, mostly when triggered in the absence of costimulatory signal. The unique T cell-specific chemokine of the C class, lymphotactin (Lptn), has recently been shown to inhibit the production of Th1-type lymphokines in human CD4(+) T cells. The present study shows the ability of Lptn to costimulate the death of CD4(+) T lymphocytes triggered through CD3/TCR. The Lptn-mediated increased cell death exhibited characteristic features of apoptosis, as mainly determined by DNA fragmentation and exposure of an apoptotic-specific mitochondrial antigen. This apoptosis was dependent on Fas/FasL signaling, was not rescued by addition of interleukin 2, and proceeded with a predominant processing of both initiator procaspase-9 and effector procaspase-7. These caspase activities were further evidenced by specific cleavage of poly(ADP-ribose) polymerase (PARP) and CD3/TCR zeta-chain, but not DNA fragmentation factor (DFF45). This study demonstrates that the functional repertoire of Lptn in the regulation of human CD4(+) T-lymphocyte activation includes the ability to costimulate apoptosis.
authors: National Institute of Health and Medical Research, University of Méditerranée and Department of Hematopathology, Institut Paoli-Calmettes, Marseille, France. cerdan@marseille.inserm.fr
authors: C
authors: C
authors: Cerdan
authors: E
authors: E
authors: Devilard
authors: L
authors: L
authors: Xerri
authors: D
authors: D
authors: Olive
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000494:pharmacology; D019744:Chemokines, C; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism; D053222:Fas Ligand Protein; D006801:Humans; D020287:In Situ Nick-End Labeling; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012795:Sialoglycoproteins / Q000494:pharmacology*; D015398:Signal Transduction; D019014:fas Receptor / Q000502:physiology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D018946:Chemokine CCL5; D019744:Chemokines, C; D015853:Cysteine Proteinase Inhibitors; D004792:Enzyme Precursors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007376:Interleukin-2; D008222:Lymphokines; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D012795:Sialoglycoproteins; C092390:XCL1 protein, human; C054979:antigen T cell receptor, zeta chain; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor; C018997:lymphotactin; D011065:Poly(ADP-ribose) Polymerases; C505520:CASP7 protein, human; C506433:CASP9 protein, human; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases