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首页> 外文期刊>Vaccine >Development of HSV-specific CD4+ Th1 responses and CD8+ cytotoxic T lymphocytes with antiviral activity by vaccination with the HSV-2 mutant ICP10 triangle PK
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Development of HSV-specific CD4+ Th1 responses and CD8+ cytotoxic T lymphocytes with antiviral activity by vaccination with the HSV-2 mutant ICP10 triangle PK

机译：通过接种HSV-2突变体ICP10三角PK疫苗开发具有抗病毒活性的HSV特异性CD4 + Th1反应和CD8 +细胞毒性T淋巴细胞

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摘要

A growth compromised herpes simplex virus type 2 (HSV-2) mutant which is deleted in the PK domain of the large subunit of ribonucleotide reductase (ICP10DeltaPK) protects from HSV-2 challenge in the mouse and guinea pig cutaneous and vaginal models and reduces the incidence and frequency of recurrent disease (Vaccine (17) (1999) 1951; Vaccine (19) (2001) 1879). The present studies were designed to identify the immune responses induced by ICP10DeltaPK and define the component responsible for protective activity. We found that ICP10DeltaPK elicits a predominant HSV-specific T helper type 1 (Th1) response, as evidenced by: (1) higher levels of HSV-specific IgG2a (Th1) than IgG1 (Th2) isotypes and (2) higher numbers of CD4+ IFN-gamma than IL-10 secreting T cells in popliteal lymph nodes. This Th1 response pattern was associated with a significant increase in the levels of IL-12 produced by dendritic cells from ICP10DeltaPK than HSV-2 immunized animals. Lymph node cells (LNCs) from ICP10DeltaPK immunized mice had significantly higher levels of HSV-2 specific cytolytic activity than LNCs from mice immunized with HSV-2 and it was mediated by CD8+ T cells. CD8+ CTL were not seen in LNCs from HSV-2 immunized mice. In adoptive transfer experiments, CD8+ T cells and, to a lower extent, CD4+ T cells from ICP10DeltaPK immunized mice inhibited HSV-2 replication, suggesting that they are involved in the protective immunity induced by ICP10DeltaPK vaccination. (C) 2002 Elsevier Science Ltd. All rights reserved. [References: 90]
机译：在核糖核苷酸还原酶大亚基的PK结构域（ICP10DeltaPK）中缺失的生长受损的2型单纯疱疹病毒2型（HSV-2）突变体可在小鼠和豚鼠的皮肤和阴道模型中保护免受HSV-2攻击并降低发病率和复发率（Vaccine（17）（1999）1951; Vaccine（19）（2001）1879）。本研究旨在确定由ICP10DeltaPK诱导的免疫应答，并确定负责保护活性的成分。我们发现ICP10DeltaPK引发了主要的HSV特异性T辅助型1（Th1）反应，这可以通过以下方面证明：（1）HSV特异性IgG2a（Th1）的水平高于IgG1（Th2）的同种型，以及（2）更高的CD4 + pop淋巴结中的IFN-γ比IL-10分泌性T细胞高。这种Th1反应模式与ICP10DeltaPK的树突状细胞相比HSV-2免疫动物的IL-12水平显着增加有关。 ICP10DeltaPK免疫小鼠的淋巴结细胞（LNC）的HSV-2特异性溶细胞活性比HSV-2免疫小鼠的LNC显着高，并且它是由CD8 + T细胞介导的。在来自HSV-2免疫小鼠的LNC中未观察到CD8 + CTL。在过继转移实验中，来自ICP10DeltaPK免疫小鼠的CD8 + T细胞和较低程度的CD4 + T细胞抑制HSV-2复制，表明它们参与了ICP10DeltaPK疫苗诱导的保护性免疫。 （C）2002 Elsevier ScienceLtd。保留所有权利。 [参考：90]

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