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
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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DOI：
10.4049/jimmunol.174.2.710
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发表时间：
2005-01-15
影响因子：
4.4
通讯作者：
Yagita, H
中科院分区：
文献类型：
--
作者：
Bullock, TNJ;Yagita, H
CD 8（+）T细胞对Ag的反应性扩增可以被表征为依赖或不依赖于CD 4（+）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。使用来自MHCIT类缺陷小鼠的树突状细胞，以避免与体内CD 4（+）T细胞的相互作用，我们比较了与感染相关的分子刺激的肽脉冲树突状细胞与通过CD 40刺激的树突状细胞的致瘤性。在没有CD 4（+）T细胞帮助的情况下，用TNF-α- poly（I：C）刺激的树突状细胞免疫后，原代CD 8（+）T细胞的扩增是最小的。相比之下，LPS或CpG刺激的树突状细胞引起了大量的初级CD 8（+）T细胞应答，尽管与用CD 40 L刺激的树突状细胞免疫产生的幅度不同。值得注意的是，用任何刺激的树突状细胞群免疫的小鼠在没有CD 4（+）T细胞帮助的情况下产生了功能齐全的回忆CD 8（+）T细胞。观察到的免疫原性等级与刺激的树突状细胞上的CD 70（CD 27 L）的表达密切相关，并且Ab介导的CD 70的阻断基本上阻止了原代CD 8（+）T细胞的CD 4（+）T细胞非依赖性扩增。这些结果表明树突状细胞上CD 70的表达是原代CD 8（+）T细胞扩增的辅助依赖性的重要决定因素，并为各种病原体在缺乏CD 4（+）T细胞的情况下刺激原代CD 8（+）T细胞应答的能力提供了解释。
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 It-deficient mice to avoid interaction with CD4(+) T cells in vivo, we have compared the inummogenicity 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-alpha- 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.