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首页> 外文期刊>The journal of immunology >Induction of CD70 on Dendritic Cells through CD40 or TLR Stimulation Contributes to the Development of CD8+ T Cell Responses in the Absence of CD4+ T Cells
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Induction of CD70 on Dendritic Cells through CD40 or TLR Stimulation Contributes to the Development of CD8+ T Cell Responses in the Absence of CD4+ T Cells

机译：在没有CD4 + T细胞的情况下，通过CD40或TLR刺激在树突状细胞上诱导CD70有助于CD8 + T细胞反应的发展。

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The expansion of CD8+ T cells in response to Ag can be characterized as either dependent or independent of CD4+ T cells. The factors that influence this dichotomy are poorly understood but may be dependent upon the degree of inflammation associated with the Ag. Using dendritic cells derived from MHC class II-deficient mice to avoid interaction with CD4+ T cells in vivo, we have compared the immunogenicity of peptide-pulsed dendritic cells stimulated with molecules associated with infection to those stimulated via CD40. In the absence of CD4+ T cell help, the expansion of primary CD8+ T cells after immunization with TNF-α- or poly(I:C)-stimulated dendritic cells was minimal. In comparison, LPS- or CpG-stimulated dendritic cells elicited substantial primary CD8+ T cell responses, though not to the same magnitude generated by immunization with CD40L-stimulated dendritic cells. Remarkably, mice immunized with any stimulated dendritic cell population generated fully functional recall CD8+ T cells without the aid of CD4+ T cell help. The observed hierarchy of immunogenicity was closely correlated with the expression of CD70 (CD27L) on the stimulated dendritic cells, and Ab-mediated blockade of CD70 substantially prevented the CD4+ T cell-independent expansion of primary CD8+ T cells. These results indicate that the expression of CD70 on dendritic cells is an important determinant for helper-dependence of primary CD8+ T cell expansion and provide an explanation for the ability of a variety of pathogens to stimulate primary CD8+ T cell responses in the absence of CD4+ T cells.
机译：响应于Ag的CD8 + T细胞的扩增可以表征为依赖或独立于CD4 + T细胞。影响这种二分法的因素知之甚少，但可能取决于与Ag相关的炎症程度。使用源自MHC II类缺陷小鼠的树突状细胞避免体内与CD4 + T细胞的相互作用，我们将与感染相关分子刺激的肽脉冲树突状细胞的免疫原性与通过CD40刺激的树突状细胞的免疫原性进行了比较。在没有CD4 + T细胞帮助的情况下，用TNF-α-或经聚（I：C）刺激的树突状细胞免疫后，原代CD8 + T细胞的扩增很小。相比之下，LPS或CpG刺激的树突状细胞可引起基本的CD8 + T细胞反应，尽管与CD40L刺激的树突状细胞免疫所产生的反应程度不同。值得注意的是，用任何刺激的树突状细胞群体免疫的小鼠在没有CD4 + T细胞帮助的情况下产生了功能全面的召回CD8 + T细胞。观察到的免疫原性等级与受激树突状细胞上CD70（CD27L）的表达密切相关，并且Ab介导的CD70阻滞作用基本上阻止了CD4 + T细胞非依赖性原代CD8 + T细胞的扩增。这些结果表明，CD70在树突状细胞中的表达是决定性依赖于初级CD8 + T细胞扩增的辅助因素，并为缺乏CD4 + T时多种病原体刺激初级CD8 + T细胞反应的能力提供了解释。细胞。

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