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用脂多糖激活的树突状细胞免疫可产生特异性的 CD8 T 细胞应答,从而对 感染提供部分保护。

Immunization With Lipopolysaccharide-Activated Dendritic Cells Generates a Specific CD8 T Cell Response That Confers Partial Protection Against Infection With .

机构信息

Instituto de Inmunología Clínica y Experimental de Rosario (IDICER), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario, Rosario, Argentina.

Centro de Investigación y Producción de Reactivos Biológicos, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.

出版信息

Front Cell Infect Microbiol. 2022 Jul 7;12:897133. doi: 10.3389/fcimb.2022.897133. eCollection 2022.

Abstract

Lipopolysaccharide (LPS) induces the activation of dendritic cells (DCs) throughout the engagement of toll-like receptor 4. LPS-activated DCs show increased capacity to process and present pathogen-derived antigens to activate naïve T cells. DCs-based vaccines have been successfully used to treat some cancer types, and lately transferred to the field of infectious diseases, in particular against HIV. However, there is no vaccine or DC therapy for any parasitic disease that is currently available. The immune response against substantially relies on T cells, and both CD4 and CD8 T lymphocytes are required to control parasite growth. Here, we develop a vaccination strategy based on DCs derived from bone marrow, activated with LPS and loaded with TsKb20, an immunodominant epitope of the trans-sialidase family of proteins. We extensively characterized the CD8 T cell response generated after immunization and compared three different readouts: a tetramer staining, ELISpot and Activation-Induced Marker (AIM) assays. To our knowledge, this work shows for the first time a proper set of T cell markers to evaluate specific CD8 T cell responses in mice. We also show that our immunization scheme confers protection against , augmenting survival and reducing parasite burden in female but not male mice. We conclude that the immunization with LPS-activated DCs has the potential to prime significant CD8 T cell responses in C57BL/6 mice independently of the sex, but this response will only be effective in female, possibly due to mice sexual dimorphisms in the response generated against .

摘要

脂多糖 (LPS) 通过与 Toll 样受体 4 的结合诱导树突状细胞 (DC) 的激活。LPS 激活的 DC 显示出增强的加工和呈递病原体衍生抗原以激活幼稚 T 细胞的能力。基于 DC 的疫苗已成功用于治疗某些癌症类型,最近已转移到传染病领域,特别是针对 HIV。然而,目前没有针对任何寄生虫病的疫苗或 DC 疗法。针对寄生虫的免疫反应主要依赖于 T 细胞,并且控制寄生虫生长既需要 CD4 也需要 CD8 T 淋巴细胞。在这里,我们开发了一种基于骨髓来源的 DC 的疫苗接种策略,该策略通过 LPS 激活并用 TsKb20 加载,TsKb20 是转唾液酸酶家族蛋白的免疫显性表位。我们广泛表征了免疫后产生的 CD8 T 细胞反应,并比较了三种不同的读出方法:四聚体染色、ELISpot 和激活诱导标志物 (AIM) 测定。据我们所知,这项工作首次显示了一组适当的 T 细胞标志物,可用于评估小鼠中的特异性 CD8 T 细胞反应。我们还表明,我们的免疫方案赋予了针对 的保护作用,提高了雌性而不是雄性小鼠的存活率并降低了寄生虫负荷。我们得出结论,用 LPS 激活的 DC 进行免疫接种有可能在 C57BL/6 小鼠中独立于性别引发显著的 CD8 T 细胞反应,但这种反应仅在雌性中有效,可能是由于针对 的反应存在小鼠性别二态性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9c/9318436/5cdb4029cbf8/fcimb-12-897133-g001.jpg

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