Differential contribution of dendritic cell CD1d to NKT cell-enhanced humoral immunity and CD8+ T cell activation

Differential contribution of dendritic cell CD1d to NKT cell-enhanced humoral immunity and CD8+ T cell activation
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DOI:
10.1189/jlb.1111559
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发表时间:
2012-05-01
影响因子:
5.5
通讯作者:
Lang, Mark L.
Lang, Mark L.
中科院分区:
医学3区
文献类型:
--
作者:
Joshi, Sunil K.;Lang, Gillian A.;Lang, Mark L.

文献摘要

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CD1d 限制的 I 型 NKT 细胞为特异性抗体的产生提供帮助。 B 细胞分别在 MHC II 类上捕获并呈递 T 依赖性抗原衍生肽和 CD1d 上结合 CD1d 的糖脂 α-GC,激活 Th 和 NKT 细胞以引发 B 细胞帮助。然而,DC CD1d 在体液免疫中的作用仍不清楚。因此,我们构建了含有表达CD1d、DTR转基因DC和CD1d(+)或CD1d(-)非转基因DC的混合骨髓嵌合体。在 DT 介导的 DC 消融和免疫后,我们观察到在 CD1d(+) 和 CD1d(-) DC 存在的情况下,一抗和二抗反应相同。相反,树突状细胞的完全消融延迟了一抗反应。进一步的实验表明,CD1d(+) DC 的耗竭可阻断抗原特异性细胞毒性 (CD8(+)) T 淋巴细胞的体内扩增。这些结果清楚地表明,尽管 DC 上的 CD1d 表达对于 NKT 增强的 CD8(+) T 细胞扩增至关重要,但对于特异性抗体的产生来说却是可有可无的。 J.洛科克。生物。 91:783-790; 2012年。
CD1d-restricted type I NKT cells provide help for specific antibody production. B cells, which have captured and presented a T-dependent, antigen-derived peptide on MHC class II and CD1d-binding glycolipid alpha-GC on CD1d, respectively, activate Th and NKT cells to elicit B cell help. However, the role of the DC CD1d in humoral immunity remains unknown. We therefore constructed mixed bone marrow chimeras containing CD1d-expressing, DTR-transgenic DCs and CD1d(+) or CD1d(-) nontransgenic DCs. Following DT-mediated DC ablation and immunization, we observed that the primary and secondary antibody responses were equivalent in the presence of CD1d(+) and CD1d(-) DCs. In contrast, a total ablation of DCs delayed the primary antibody response. Further experiments revealed that depletion of CD1d(+) DCs blocked in vivo expansion of antigen-specific cytotoxic (CD8(+)) T lymphocytes. These results provide a clear demonstration that although CD1d expression on DCs is essential for NKT-enhanced CD8(+) T cell expansion, it is dispensable for specific antibody production. J. Leukoc. Biol. 91: 783-790; 2012.