title: CC chemokine ligand 25 enhances resistance to apoptosis in CD4+ T cells from patients with T-cell lineage acute and chronic lymphocytic leukemia by means of livin activation.
abstract: We investigated CD4 and CD8 double-positive thymocytes, CD4(+) T cells from typical patients with T-cell lineage acute lymphocytic leukemia (T-ALL) and T cell lineage chronic lymphocytic leukemia (T-CLL), and MOLT4 T cells in terms of CC chemokine ligand 25 (CCL25) functions of induction of resistance to tumor necrosis factor alpha (TNF-alpha)-mediated apoptosis. We found that CCL25 selectively enhanced resistance to TNF-alpha-mediated apoptosis in T-ALL and T-CLL CD4(+) T cells as well as in MOLT4 T cells, but CD4 and CD8 double-positive thymocytes did not. One member protein of the inhibitor of apoptosis protein (IAP) family, Livin, was selectively expressed in the malignant cells at higher levels, particularly in T-ALL CD4(+) T cells, in comparison with the expression in CD4 and CD8 double-positive thymocytes. After stimulation with CCL25 and apoptotic induction with TNF-alpha, the expression levels of Livin in these malignant cells were significantly increased. CCL25/thymus-expressed chemokine (TECK), by means of CC chemokine receptor 9 (CCR9) ligation, selectively activated Livin to enhance resistance to TNF-alpha-mediated apoptosis in c-jun-NH(2)-kinase 1 (JNK1) kinase-dependent manner. These findings suggested differential functions of CCR9/CCL25 in distinct types of cells. CD4 and CD8 double-positive thymocytes used CCR9/CCL25 for migration, homing, development, maturation, selection, cell homeostasis, whereas malignant cells, particularly T-ALL CD4(+) T cells, used CCR9/CCL25 for infiltration, resistance to apoptosis, and inappropriate proliferation.
authors.affiliation: Department of Immunology, and Laboratory of Allergy and Clinical Immunology, Institute of Allergy and Immune-related Diseases and Center for Medical Research, Wuhan University School of Medicine, Wuhan, Republic of China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Qiuping
authors.forename: Xiong
authors.initials: X
authors.lastname: Jei
authors.forename: Jin
authors.initials: J
authors.lastname: Youxin
authors.forename: Ju
authors.initials: J
authors.lastname: Wei
authors.forename: Liu
authors.initials: L
authors.lastname: Chun
authors.forename: Wang
authors.initials: W
authors.lastname: Jin
authors.forename: Wu
authors.initials: W
authors.lastname: Qun
authors.forename: Liu
authors.initials: L
authors.lastname: Yan
authors.forename: Hu
authors.initials: H
authors.lastname: Chunsong
authors.forename: Yang
authors.initials: Y
authors.lastname: Mingzhen
authors.forename: Gao
authors.initials: G
authors.lastname: Qingping
authors.forename: Zhang
authors.initials: Z
authors.lastname: Kejian
authors.forename: Sun
authors.initials: S
authors.lastname: Zhimin
authors.forename: Li
authors.initials: L
authors.lastname: Qun
authors.forename: Liu
authors.initials: L
authors.lastname: Junyan
authors.forename: Tan
authors.initials: T
authors.lastname: Jinquan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D019742:Chemokines, CC / Q000276:immunology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D015461:Leukemia, Prolymphocytic, T-Cell / Q000276:immunology* / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000473:pathology; D048055:Mitogen-Activated Protein Kinase 8 / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; D019742:Chemokines, CC; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D048055:Mitogen-Activated Protein Kinase 8