CD1d-restricted T cells license B cells to generate long-lasting cytotoxic antitumor immunity in vivo
CD1d-restricted T cells license B cells to generate long-lasting cytotoxic antitumor immunity in vivo
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DOI：
10.1158/0008-5472.can-06-0889
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发表时间：
2006-07-01
期刊：
影响因子：
11.2
通讯作者：
Kang, Chang-Yuil
中科院分区：
文献类型：
--
作者：
Chung, Yeonseok;Kim, Byung-Seok;Kang, Chang-Yuil
尽管众所周知，静息 B 细胞的免疫原性较差，并且会诱导 T 细胞耐受，但我们在这里尝试测试它们的免疫原性是否可以通过 CD1d 限制性不变 T 细胞 (iNKT) 增强到可用于细胞疫苗的程度。我们发现，向负载肽的 B 细胞添加 iNKT 配体 α-半乳糖神经酰胺 (α GalCer) 克服了肽特异性 T 细胞无反应性，并允许产生肽特异性记忆 CTL 免疫。该 CTL 的诱导独立于 CD4 T 和自然杀伤细胞，但需要 iNKT 和 CD8 T 细胞。 B 细胞直接引发 CTL，并且 α GalCer 和肽必须呈递在同一细胞上。重要的是，我们基于 B 细胞的疫苗在效率上与基于树突细胞的疫苗相当，可诱导类似的 CTL 反应，并提供有效的方案来预防和抑制皮下感染。和转移性肿瘤。因此，在 iNKT 的帮助下，肽脉冲 B 细胞可以建立持久的抗肿瘤免疫力，因此有望成为替代细胞疫苗的基础。
Although resting B cells are known for being poorly immunogenic and for inducing T-cell tolerance, we have here attempted to test whether their immunogenicity could be enhanced by CD1d-restricted invariant T cells (iNKT) to a point where they could be used in cellular vaccines. We found that the addition of the iNKT ligand alpha-galactosylceramide (alpha GalCer) to peptide-loaded B cells overcame peptide-specific T-cell unresponsiveness and allowed for the generation of peptide-specific memory CTL immunity. This CTL was induced independently of CD4 T and natural killer cells but required iNKT and CD8 T cells. B cells directly primed CTL, and the alpha GalCer and the peptide must be presented on the same cell. Importantly, our B-cell-based vaccine is comparable in efficiency with dendritic cell-based vaccines, inducing similar CTL responses as well as providing an effective regimen for preventing and suppressing s.c. and metastatic tumors. Therefore, with the help of iNKT, peptide-pulsed B cells can establish long-lasting antitumor immunity and so show promise as the basis for an alternative cell-based vaccine.