title: A perforin/granzyme-positive MDS-derived T cell line, K2-MDS, induces apoptosis in CD34+ cells through the fractalkine-CX3CR1 system.
abstract: Fractalkine (CX3CL1) and its receptor CX3CR1 play an important role in natural killer (NK) cell- and cytotoxic T cell-mediated endothelium damage. Here we describe the cytotoxicity of myelodysplastic syndrome (MDS)-derived T cell line, K2-MDS, through the fractalkine-CX3CR1 system. K2-MDS cells induced apoptosis against CD34(+) cells from normal bone marrow (BM) in a direct cell contact manner. K2-MDS cells expressed perforin and granzyme B, but they lacked Fas ligand expression. A specific inhibitor for perforin, concanamycin A, blocked K2-MDS-dependent cytotoxicity. Furthermore, a CX3C-chemokine, fractalkine, was expressed in CD34(+) cells, and its receptor, CX3CR1, was expressed on K2-MDS cells. The neutralizing monoclonal antibody (MoAb) for fractalkine and soluble fractalkine significantly inhibited K2-MDS-dependent cytotoxicity. K2-MDS cells also induced the cytotoxicity against human umbilical cord endothelial cells (HUVECs) expressing fractalkine. These data indicate that K2-MDS may be a perforin-granzyme-positive T cell line that exerts a cytotoxic effect on CD34(+) cells mediated through the fractalkine-CX3CR1 system.
authors.affiliation: Division of Hematology, Nephrology and Rheumatology, Department of Internal Medicine, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Morita
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Matsuda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hanamoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tatsumi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kanamaru
mesh_terms: D018952:Antigens, CD34 / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D002460:Cell Line; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism*; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019707:Receptors, Chemokine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D018952:Antigens, CD34; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D019707:Receptors, Chemokine