Qiuping Zhang, Jie Xiong, Youxin Jin, Qun Wu, Wei Ju, Chun Liu, Jin Wang, Yan Liu, Chunsong Hu, Mingzhen Yang, Qingping Gao, Qun Li, Kejian Zhang, Zhimin Sun, Junyan Liu, Jinquan Tan
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.
Oncogene. 2005 Jan 20;24(4):573-84. doi: 10.1038/sj.onc.1208184.
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.
我们从脐带血以及典型的T细胞系急性淋巴细胞白血病和T细胞系慢性淋巴细胞白血病患者中分离出CD4(+)CD34(+)、CD8(+)CD34(+)、CD4(+)CD34(-)和CD8(+)CD34(-) T细胞，研究其CXCR5/CXCL13的表达及功能。我们发现，CXCR5在T细胞系急性（慢性）淋巴细胞白血病（T-ALL）的CD8(+)CD34(+) T细胞上选择性高表达，但在T-ALL的CD4(+)CD34(+)、CD4(+)CD34(-)和CD8(+)CD34(-) T细胞上不表达。CXCR5在所有类型的CD34(+)和CD34(-)脐带血或T-CLL T细胞上均很少表达。CXCL13/B细胞趋化因子1可诱导T-ALL的CD8(+)CD34(+) T细胞对TNF-α介导的凋亡产生显著抗性，而非诱导趋化和黏附反应。CXCL13/BCA-1（B细胞趋化因子1）可上调T-ALL的CD8(+)CD34(+) T细胞中增殖诱导配体的表达。通过激活增殖诱导配体，CXCR5/CXCL13对可诱导T-ALL的CD8(+)CD34(+) T细胞以livin依赖的方式产生抗凋亡作用。在此过程中，培养中的细胞间接触是必要的。基于我们的研究结果，我们认为CXCR5/CXCL13在不同类型的细胞中具有不同的功能。正常淋巴细胞，尤其是初始B细胞和T细胞，利用CXCR5/CXCL13进行迁移、归巢、成熟和细胞稳态维持，以及二级淋巴组织器官发生。与此同时，某些恶性细胞利用CXCR5/CXCL13进行浸润、抗凋亡和异常增殖。
