Department of Surgery, Comprehensive Transplant Center, The Ohio State University, Columbus, OH.
Medical Student Research Program, The Ohio State University College of Medicine, Columbus, OH.
Transplantation. 2019 Sep;103(9):1809-1820. doi: 10.1097/TP.0000000000002683.
We previously reported the novel activity of alloprimed CD8 T cells that suppress posttransplant alloantibody production. The purpose of the study is to investigate the expression and role of CXCR5 on antibody-suppressor CD8 T-cell function.
C57BL/6 mice were transplanted with FVB/N hepatocytes. Alloprimed CD8 T cells were retrieved on day 7 from hepatocyte transplant recipients. Unsorted or flow-sorted (CXCR5CXCR3 and CXCR3CXCR5) alloprimed CD8 T-cell subsets were analyzed for in vitro cytotoxicity and capacity to inhibit in vivo alloantibody production following adoptive transfer into C57BL/6 or high alloantibody-producing CD8 knock out (KO) hepatocyte transplant recipients. Alloantibody titer was assessed in CD8 KO mice reconstituted with naive CD8 T cells retrieved from C57BL/6, CXCR5 KO, or CXCR3 KO mice. Antibody suppression by ovalbumin (OVA)-primed monoclonal OVA-specific t-cell receptor transgenic CD8+ T cells (OT-I) CXCR5 or CXCR3 CD8 T-cell subsets was also investigated.
Alloprimed CXCR5CXCR3CD8 T cells mediated in vitro cytotoxicity of alloprimed "self" B cells, while CXCR3CXCR5CD8 T cells did not. Only flow-sorted alloprimed CXCR5CXCR3CD8 T cells (not flow-sorted alloprimed CXCR3CXCR5CD8 T cells) suppressed alloantibody production and enhanced graft survival when transferred into transplant recipients. Unlike CD8 T cells from wild-type or CXCR3 KO mice, CD8 T cells from CXCR5 KO mice do not develop alloantibody-suppressor function. Similarly, only flow-sorted CXCR5CXCR3 (and not CXCR3CXCR5) OVA-primed OT-I CD8 T cells mediated in vivo suppression of anti-OVA antibody production.
These data support the conclusion that expression of CXCR5 by antigen-primed CD8 T cells is critical for the function of antibody-suppressor CD8 T cells.
我们之前报道了别嘌呤醇激活的 CD8 T 细胞具有抑制移植后同种抗体产生的新功能。本研究旨在探讨 CXCR5 在抗体抑制性 CD8 T 细胞功能上的表达和作用。
将 C57BL/6 小鼠移植 FVB/N 肝细胞。在肝细胞移植受体第 7 天回收别嘌呤醇激活的 CD8 T 细胞。分析未分选或流式细胞分选（CXCR5CXCR3 和 CXCR3CXCR5）的别嘌呤醇激活的 CD8 T 细胞亚群的体外细胞毒性，并分析其在过继转移到 C57BL/6 或高同种抗体产生的 CD8 敲除（KO）肝细胞移植受体后的体内抑制同种抗体产生的能力。用从小鼠体内回收的幼稚 CD8 T 细胞重建 CD8 KO 小鼠，这些小鼠来源于 C57BL/6、CXCR5 KO 或 CXCR3 KO 小鼠。还研究了卵清蛋白（OVA）激活的单克隆 OVA 特异性 T 细胞受体转基因 CD8+T 细胞（OT-I）CXCR5 或 CXCR3 CD8 T 细胞亚群的抗体抑制作用。
别嘌呤醇激活的 CXCR5CXCR3CD8 T 细胞介导同种异体激活的“自身”B 细胞的体外细胞毒性，而 CXCR3CXCR5CD8 T 细胞则没有。只有流式细胞分选的别嘌呤醇激活的 CXCR5CXCR3CD8 T 细胞（而非流式细胞分选的别嘌呤醇激活的 CXCR3CXCR5CD8 T 细胞）在转移到移植受体中时，既能抑制同种抗体的产生，又能提高移植物的存活率。与野生型或 CXCR3 KO 小鼠的 CD8 T 细胞不同，CXCR5 KO 小鼠的 CD8 T 细胞不能产生同种抗体抑制功能。同样，只有流式细胞分选的 CXCR5CXCR3（而非 CXCR3CXCR5）OVA 激活的 OT-I CD8 T 细胞介导体内抗 OVA 抗体产生的抑制作用。
这些数据支持这样的结论，即抗原激活的 CD8 T 细胞表达 CXCR5 对于抗体抑制性 CD8 T 细胞的功能至关重要。
