Jiang Hang, Li Linhai, Han Jiang, Sun Zhiwei, Rong Yihui, Jin Yun
1 Department of Hepatobiliary Surgery, Kunming General Hospital of PLA , Kunming, China .
2 Department of The First General Surgery, The First People's Hospital of Yunnan Province , Kunming, China .
DNA Cell Biol. 2017 Apr;36(4):321-327. doi: 10.1089/dna.2016.3571. Epub 2017 Feb 3.
Treatment options for chronic hepatitis B (CHB) infection are extremely limited. CXCR5 CD8 T cell is a novel cell subtype and could possess strong cytotoxic properties in HIV infection. In this study, we investigated the role of CXCR5 CD8 T cells in CHB patients. Compared to healthy individuals, both CHB patients and hepatitis B virus (HBV)-infected hepatocellular carcinoma patients presented significant upregulation of CXCR5 CD8 T cells in peripheral blood, in which CXCR5 CD8 T cells were negatively correlated with the frequency of CXCR5 CD4 T cells in CHB patients. After PMA+ionomycin stimulation, CXCR5 CD8 T cells from CHB patients presented significantly higher transcription level of interferon gamma (IFN-γ), interleukin 10 (IL-10), and IL-21, as well as higher IL-10 and IL-21 protein secretion, than CXCR5 CD8 T cells. Unlike CXCR5 CD4 T cells, when incubated with naive CD19CD27 B cells, CXCR5 CD8 T cells alone did not upregulate IgM, IgG, and IgA secretion. However, addition of CXCR5 CD8 T cells in B cell-CXCR5 CD4 T cell coculture significantly increased the levels of secreted IgG and IgA, demonstrating that CXCR5 CD8 T cell could indirectly offer B cell help. Furthermore, high frequencies of CXCR5 CD8 T cells tended to associate with low HBV DNA load, and the frequency of CXCR5 CD8 T cells was negatively correlated with alanine aminotransferase (ALT) level. Together, these results suggested that CXCR5 CD8 T cells were involved in the antiviral immune responses in CHB and could potentially serve as a therapeutic candidate.
慢性乙型肝炎（CHB）感染的治疗选择极为有限。CXCR5 CD8 T细胞是一种新型细胞亚型，在HIV感染中可能具有强大的细胞毒性特性。在本研究中，我们调查了CXCR5 CD8 T细胞在CHB患者中的作用。与健康个体相比，CHB患者和乙型肝炎病毒（HBV）感染的肝细胞癌患者外周血中CXCR5 CD8 T细胞均显著上调，其中CHB患者中CXCR5 CD8 T细胞与CXCR5 CD4 T细胞频率呈负相关。经佛波酯（PMA）+离子霉素刺激后，CHB患者的CXCR5 CD8 T细胞比CXCR5 CD8 T细胞呈现出显著更高的干扰素γ（IFN-γ）、白细胞介素10（IL-10）和IL-21转录水平，以及更高的IL-10和IL-21蛋白分泌。与CXCR5 CD4 T细胞不同，当与初始CD19CD27 B细胞共孵育时，单独的CXCR5 CD8 T细胞不会上调IgM、IgG和IgA分泌。然而，在B细胞-CXCR5 CD4 T细胞共培养中添加CXCR5 CD8 T细胞可显著提高分泌的IgG和IgA水平，表明CXCR5 CD8 T细胞可间接提供B细胞辅助。此外，高频率的CXCR5 CD8 T细胞往往与低HBV DNA载量相关，且CXCR5 CD8 T细胞频率与丙氨酸转氨酶（ALT）水平呈负相关。总之，这些结果表明CXCR5 CD8 T细胞参与了CHB的抗病毒免疫反应，并有可能作为一种治疗候选物。
