抗体抑制性 CD8+ T 细胞需要 CXCR5。
Antibody-suppressor CD8+ T Cells Require CXCR5.
机构信息
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.
出版信息
Transplantation. 2019 Sep;103(9):1809-1820. doi: 10.1097/TP.0000000000002683.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
背景
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。
方法
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。
结果
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。
结论
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。
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