CD8+ T cells are crucial for humoral immunity establishment by SA14‐14‐2 live attenuated Japanese encephalitis vaccine in mice,European Journal of Immunology

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CD8+ T cells are crucial for humoral immunity establishment by SA14‐14‐2 live attenuated Japanese encephalitis vaccine in mice
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-08-04 , DOI: 10.1002/eji.202048745
Anurag Kalia ₁ , Mona Agrawal ₁ , Nimesh Gupta ₁

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The live attenuated SA14‐14‐2 Japanese encephalitis (JE) vaccine is a historical vaccine that protects against JE. Despite its extensive use, the mechanism of protective immunity conferred by the SA14‐14‐2 vaccine is not well established. Here, we used mouse models to understand the mechanism of the development of humoral immunity against the vaccine. The vaccine induces robust GC responses within a week postimmunization. In lethal virus challenge, we show that CD4⁺ T cells alone, but not CD8⁺ T cells, are sufficient to confer vaccine‐mediated protection. However, the CD4‐mediated protection was potentiated in the presence of vaccine‐primed CD8⁺ T cells. Employing CD8‐deficient mice, we show that both the protective traits of CD4⁺ T cells and the quality of antibody response to the vaccine are impaired in absence of CD8⁺ T cells. We further demonstrate that the poor protective immune response induced by the vaccine in absence of CD8⁺ T cells is mainly due to the impaired differentiation and function of follicular Th cells, leading to suboptimal GC reaction. Our study highlights an unprecedented role of CD8⁺ T cells in the establishment of humoral responses to the vaccine. By elucidating underlying cellular determinants of vaccine‐induced protective immunity, our work has implications for rational design of vaccines against JE virus and related flaviviruses.

中文翻译：

CD8 + T细胞对于SA14-14-2减毒日本脑炎活疫苗在小鼠体内建立体液免疫至关重要

SA14-14-2减毒活日本脑炎（JE）疫苗是一种预防JE的历史性疫苗。尽管已广泛使用，但SA14-14-2疫苗赋予的保护性免疫机制尚未完全确立。在这里，我们使用小鼠模型来了解针对疫苗的体液免疫发展的机制。疫苗在免疫后一周内诱导强烈的GC反应。在致命病毒攻击中，我们证明仅CD4 ⁺ T细胞就足以提供疫苗介导的保护，而CD8 ⁺ T细胞不足。但是，在存在疫苗引发的CD8 ⁺ T细胞的情况下，CD4介导的保护作用得到加强。利用CD8缺陷型小鼠，我们发现CD4 ^+的两种保护性状在没有CD8 ⁺ T细胞的情况下，T细胞和对疫苗的抗体反应质量受到损害。我们进一步证明，在没有CD8 ⁺ T细胞的情况下，疫苗诱导的保护性免疫应答较差，主要是由于滤泡Th细胞的分化和功能受损，导致了次优的GC反应。我们的研究突出了CD8 ⁺ T细胞在建立疫苗体液反应中的空前作用。通过阐明疫苗诱导的保护性免疫的基本细胞决定因素，我们的工作对合理设计针对JE病毒和相关黄病毒的疫苗具有重要意义。

更新日期：2020-08-04

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