Selectively frequent expression of CXCR5 enhances resistance to apoptosis in CD8+CD34+ T cells from patients with T-cell-lineage acute lymphocytic leukemia

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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-α-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 naïve 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.