title: CD99 signals caspase-independent T cell death.
abstract: Death signaling by Fas and TNF receptors plays a major role in the control of activated mature T cells. However, the nature of the death receptors, which may be used by the immune system to control T cells that have not acquired susceptibility to Fas ligand or TNF, is not established. In this study, we demonstrate that engagement of distinct epitopes on CD99 rapidly induces T cell death by a novel caspase-independent pathway. A new mAb to these CD99 epitopes, Ad20, induces programmed cell death of transformed T cells as determined by morphological changes, phosphatidylserine exposure on the cell surface, and uptake of propidium iodide. In general, ligation of CD99 induced kinetically faster and more profound death responses as compared with the impact of anti-Fas and TNF-related apoptosis-inducing ligand (TRAIL). Ad20-induced programmed cell death was observed with seven of eight T cell lines examined, and notably, only two of these were distinctly responsive to anti-Fas and TRAIL. CD99-mediated death signaling proceeded independently of functional CD3, CD4, CD45, and p56(lck), revealed distinctions from CD47-mediated T cell death responses, and was not influenced by interference with CD47 signaling. In contrast to the effect on transformed T cell lines, Ad20-induced death responses were not observed with normal peripheral T cells. Thus, our data suggest that CD99 is linked to a novel death pathway that may have biologic relevance in control of early T cells.
authors: Department of Pediatric Research and Pediatrics, National Hospital, Oslo, Norway. rolf.pettersen@klinmed.uio.no
authors: R D
authors: RD
authors: Pettersen
authors: G
authors: G
authors: Bernard
authors: M K
authors: MK
authors: Olafsen
authors: M
authors: M
authors: Pourtein
authors: S O
authors: SO
authors: Lie
mesh_terms: D000071443:12E7 Antigen; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D051928:CD47 Antigen; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D020169:Caspases / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D006224:Cricetinae; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D008024:Ligands; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells; D019014:fas Receptor / Q000276:immunology
chemical_list: D000071443:12E7 Antigen; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D051928:CD47 Antigen; C497894:CD47 protein, human; C061828:CD99 protein, human; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D008024:Ligands; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D020169:Caspases