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慢性乙型肝炎和慢性丙型肝炎的肝内免疫浸润:相似但不相同。

Intrahepatic immune infiltrate in chronic hepatitis B and chronic hepatitis C: Similar but not the same.

机构信息

Pathology Division, Laboratory of Molecular Biology, Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA, Ricardo Gutiérrez Children's Hospital, CABA, Argentina.

Liver Unit, Italian's Hospital of Buenos Aires, CABA, Argentina.

出版信息

J Viral Hepat. 2022 Feb;29(2):124-134. doi: 10.1111/jvh.13635. Epub 2021 Nov 28.

Abstract

In chronic hepatitis B (CHB) and C (CHC) infections, the composition of the immune cell microenvironment at the site of infection is poorly understood. Thus, our aim was to characterize and compare liver infiltrates to identify shared and exclusive hepatic immune components. Immunohistochemistry was performed on 26 CHB and 42 CHC liver biopsies to determine Th (CD4+), Th1 (T-bet+), Th17 (IL-17A+), Treg (Foxp3+) and CTL (CD8+) cells frequency in portal/periportal and intralobular areas and relate them to liver damage. CHB and CHC cases shared a portal/periportal CD4+ lymphocyte predominance and a lobular CD8+ lymphocyte majority. However, CHC exhibited a concomitant lobular T-bet+ cell dominance while in CHB FoxP3+ cells prevail. CHC disclosed higher frequencies of P/P FoxP3+, IL-17A+ and T-bet+ cells and intralobular CD4+, IL-17A+ and T-bet+ lymphocytes. HBeAg+ chronic hepatitis and CHC cell frequencies were similar except for lobular T-bet+ that remained higher among CHC cases. Comparison among cases with less severe liver disease revealed lower lymphocyte frequencies in CHB samples, while no differences were observed between patients with more severe stages. Interestingly, in CHB portal/periportal CD4+ and lobular CD4+, CD8+ and IL-17A+ cells were associated with severe hepatitis. Even when all studied populations were identified in both infections preferential lymphocyte frequencies and prevalence at different areas along with their association with liver damage highlighted that CHB and CHC immune responses are not the same.

摘要

在慢性乙型肝炎 (CHB) 和丙型肝炎 (CHC) 感染中,感染部位免疫细胞微环境的组成尚不清楚。因此,我们的目的是对肝脏浸润物进行特征分析和比较,以确定共同和独特的肝脏免疫成分。对 26 例 CHB 和 42 例 CHC 肝活检进行免疫组织化学染色,以确定门脉/周围和小叶内区域中 Th(CD4+)、Th1(T-bet+)、Th17(IL-17A+)、Treg(Foxp3+)和 CTL(CD8+)细胞的频率,并将其与肝损伤相关联。CHB 和 CHC 病例均具有门脉/周围 CD4+淋巴细胞优势和小叶内 CD8+淋巴细胞优势。然而,CHC 同时表现为小叶内 T-bet+细胞优势,而在 CHB 中 Foxp3+细胞占优势。CHC 显示出更高频率的 P/P Foxp3+、IL-17A+和 T-bet+细胞以及小叶内 CD4+、IL-17A+和 T-bet+淋巴细胞。HBeAg+慢性肝炎和 CHC 细胞频率相似,但小叶内 T-bet+细胞除外,CHC 病例中该细胞频率更高。在疾病较轻的病例中进行比较时,CHB 样本中的淋巴细胞频率较低,而在病情较重的患者中则没有差异。有趣的是,在 CHB 中门脉/周围 CD4+和小叶内 CD4+、CD8+和 IL-17A+细胞与严重肝炎相关。即使在两种感染中都发现了所有研究人群,不同区域的淋巴细胞优势频率和流行率及其与肝损伤的相关性也表明 CHB 和 CHC 的免疫反应并不相同。

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