CXCL13-mediated recruitment of intrahepatic CXCR5+CD8+ T cells favors viral control in chronic HBV infection

Li, Yongyin; Tang, Libo; Guo, Ling; Chen, Chengcong; Gu, Shuqin; Zhou, Yang; Ye, Guofu; Li, Xiaohua; Wang, Weibin; Liao, Xinxin; Wang, Yu; Peng, Xiaohong; Liu, Guangze; Zhang, Xiaoyong; Sun, Jian; Peng, Jie; Hou, Jinlin

doi:10.1016/j.jhep.2019.09.031

Cited by 75 publications

(98 citation statements)

References 34 publications

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“…We also observed that CXCR5 + CD8 + T cells, a unique population that differs from traditional CD8 + T cells, have a greater ability to suppress HBV and facilitate B cells to produce HBV-speci c antibodies by secreting IL-21 [11]. However, the characteristics and functions of FDCs in patients with chronic HBV infection remain largely unknown.…”

Section: Introductionmentioning

confidence: 85%

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Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

Zhang

Zhang³

et al. 2020

Preprint

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Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4+ T cells and CD19+ B cells. Results: We observed that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared to that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, positive correlations were observed between the frequencies of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5)+CD4+ T cells and CXCR5+CD8+ T cells. Notably, in vitro experimental results demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4+ T cells and promoted the proliferation of autologous intrasplenic CD19+ B cells.Conclusions: Expanded FDCs in patients with chronic HBV infection may favor host immune responses against HBV. The identification of this unique population of cell may contribute to a better understanding of the immune regulatory mechanisms associated with chronic HBV infection and provide a potential immunotherapeutic target for this disease.

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Section: Introductionmentioning

confidence: 85%

“…Human SMCs were isolated as previously described [11,21]. Brie y, the splenic tissue samples (2 cm 3 ) were placed into a 70-μm nylon mesh lter in a culture dish with medium, and then the rounded side of a plunger from a 10 mL syringe was used to mechanically crush the tissues.…”

Section: Mononuclear Cells Isolationmentioning

confidence: 99%

Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

Zhang

Zhang³

et al. 2020

Preprint

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“…Humoral immune responses play an essential role in the control of viral infection. However, previous studies have documented a comprised HBsAg-speci c B cell response in patients with chronic HBV infection [10,11], and the reversal of B-cell functional impairment is associated with HBsAg seroconversion [23]. Of note, it has been reported that FDCs are essential for B cell survival and motivate the process of a nity maturation during GC reaction [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, PBMCs and HMCs were isolated by density-gradient centrifugation on Ficoll-Hypaque and were cryopreserved in liquid nitrogen. Human SMCs were isolated as previously described [11,19]. Brie y, the splenic tissues (2 cm 3 ) were placed into a 70 μm nylon mesh lter in a culture dish with the medium, and then the rounded side of a plunger from a 10 mL syringe was used to crush the tissues mechanically.…”

Section: Mononuclear Cells Isolationmentioning

confidence: 99%

“…However, there was no signi cant correlation existed between the frequency of intrasplenic FDCs and intrasplenic B cell subsets (Additional le 1: Figure S1). Moreover, as CXCR5 + CD4 + T cells and CXCR5 + CD8 + T cells are critical for GC immune responses [10,11], we further investigated the frequencies of these two subpopulations in peripheral blood and spleen. Importantly, we found that the frequency of circulating FDCs was positively correlated with the frequencies of CXCR5 + CD4 + T cells and CXCR5 + CD8 + T cells (Fig.…”

Section: A Positive Correlation Between the Frequency Of Circulating mentioning

confidence: 99%

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Expanded Circulating Follicular Dendritic Cells Facilitate Immune Responses in Chronic HBV Infection

Zhang

Zhang³

et al. 2020

Preprint

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Background: Restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. This study aims to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4+ T cells and CD19+ B cells. Results: We found that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared with that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, a positive correlation between the frequency of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5)+CD4+ T cells and CXCR5+CD8+ T cells was also observed. Notably, in vitro experiments demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4+ T cells and promoted the proliferation of autologous intrasplenic CD19+ B cells.Conclusions: Expanded FDCs in patients with chronic HBV infection may favor the host immune responses against HBV. The identification of this unique population may contribute to a better understanding of the immune regulatory mechanisms and provide a potential immunotherapeutic target in chronic HBV infection.

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Efficacy and safety of a nanoparticle therapeutic vaccine in patients with chronic hepatitis B: A randomized clinical trial

Wei

Zhao²,

et al. 2021

Hepatology

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Background and Aim: HBV DNA can be reduced using antiviral drugs in patients with chronic hepatitis B (CHB); however, the rate of HBeAg seroconversion remains low. A clinical trial was conducted to assess the efficacy and safety of a de novo designed liposome-based nanoparticle lipopeptide vaccine, εPA-44, for CHB. Approach and Results: A two-stage phase 2 trial, which included a 76week, randomized, double-blind, placebo-controlled trial (stage 1) and a 68week open-label extension (stage 2), was conducted in 15 centers across China (Clinicaltrials.gov No. NCT00869778). In stage 1, 360 human leukocyte | 183 HEPATOLOGY

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CXCL13-mediated recruitment of intrahepatic CXCR5+CD8+ T cells favors viral control in chronic HBV infection

Cited by 75 publications

References 34 publications

Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

Expanded Circulating Follicular Dendritic Cells Facilitate Immune Responses in Chronic HBV Infection

Efficacy and safety of a nanoparticle therapeutic vaccine in patients with chronic hepatitis B: A randomized clinical trial

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