title: Selectively frequent expression of CXCR5 enhances resistance to apoptosis in CD8(+)CD34(+) T cells from patients with T-cell-lineage acute lymphocytic leukemia.
abstract: We investigated CD4(+)CD34(+), CD8(+)CD34(+), CD4(+)CD34(-), and CD8(+)CD34(-) T cells from cord blood and from typical patients with T-cell-lineage acute lymphocytic leukemia and T-cell-lineage chronic lymphocytic leukemia in terms of expression and functions of CXCR5/CXCL13. We found that CXCR5 was selectively frequently expressed on T-cell-lineage acute (chronic) lymphocytic leukemia (T-ALL) CD8(+)CD34(+) T cells, but not on T-ALL CD4(+)CD34(+), CD4(+)CD34(-), and CD8(+)CD34(-) T cells. CXCR5 was rarely expressed on all types of CD34(+) and CD34(-) CB or T-CLL T cells. CXCL13/B cells attracting chemokine 1 induced significant resistance to TNF-alpha-mediated apoptosis in T-ALL CD8(+)CD34(+) T cells, instead of induction of chemotactic and adhesive responsiveness. A proliferation-inducing ligand expression in T-ALL CD8(+)CD34(+) T cells was upregulated by CXCL13/BCA-1 (B-cell attracting chemokine 1). The CXCR5/CXCL13 pair by means of activation of APRIL (A proliferation-inducing ligand) induced resistance to apoptosis in T-ALL CD8(+)CD34(+) T cells in livin-dependent manner. In this process, cell-cell contact in culture was necessary. Based on our findings, we suggested that there were differential functions of CXCR5/CXCL13 in distinct types of cells. Normal lymphocytes, especially naive B and T cells, utilized CXCR5/CXCL13 for migration, homing, maturation, and cell homeostasis, as well as secondary lymphoid tissue organogenesis. Meanwhile, certain malignant cells took advantages of CXCR5/CXCL13 for infiltration, resistance to apoptosis, and inappropriate proliferation.
authors.affiliation: Department of Immunology, Institute of Allergy and Immune-related Diseases, Centre for Medical Research, Wuhan University School of Medicine, Wuhan University, Dong Hu Road 115, Wuchang, Wuhan 430071, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Qiuping
authors.forename: Xiong
authors.initials: X
authors.lastname: Jie
authors.forename: Jin
authors.initials: J
authors.lastname: Youxin
authors.forename: Wu
authors.initials: W
authors.lastname: Qun
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: 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: Li
authors.initials: L
authors.lastname: Qun
authors.forename: Zhang
authors.initials: Z
authors.lastname: Kejian
authors.forename: Sun
authors.initials: S
authors.lastname: Zhimin
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 / Q000235:genetics / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000378:metabolism / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000235:genetics
chemical_list: C490341:ANP32B protein, human; D048868:Adaptor Proteins, Signal Transducing; D018952:Antigens, CD34; C419866:BIRC7 protein, human; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D014409:Tumor Necrosis Factor-alpha