Mechanism of NK cell activation induced by coculture with dendritic cells derived from peripheral blood monocytes
Mechanism of NK cell activation induced by coculture with dendritic cells derived from peripheral blood monocytes
复制标题
DOI：
10.1046/j.1365-2249.2001.01550.x
复制
发表时间：
2001-05-01
影响因子：
4.6
通讯作者：
Bamba, T
中科院分区：
文献类型：
--
作者：
Amakata, Y;Fujiyama, Y;Bamba, T
树突状细胞（Dendritic cells，DCs）被认为是一种有效的抗原提呈细胞，但DCs与淋巴细胞尤其是自然杀伤细胞（natural killer，NK细胞）的关系尚不清楚。在这项研究中，我们评估了DC如何相互作用的淋巴细胞和NK细胞使用共培养系统。当与DC共培养时，淋巴细胞的数量显著增加（增加1.8倍）。特别是NK细胞的增殖显著。此外，DC与淋巴细胞的共培养诱导IL-12和IFN-γ分泌的显著增加。当DC和淋巴细胞之间的接触被阻止时，IL-12和IFN-γ的分泌显著减少。IFN-γ产生被抗IL-12抗体完全阻断，表明IFN-γ分泌依赖于IL-12分泌。DC对淋巴细胞增殖的刺激作用被抗IL-12抗体部分抑制，并且当细胞接触被阻止时完全减弱。CD 40-CD 40 L或CD 28-B7分子的相互作用可显著抑制DC诱导的NK细胞增殖。与DC的共培养使NK活性增强40%，并且这被抗IL-12抗体部分抑制，并且被细胞间接触的抑制完全阻断。这些结果表明，DC对NK细胞的活化部分由IL-12分泌介导，并且DC与NK细胞之间的直接接触在这种应答中起主要作用。
Dendritic cells (DCs) have been regarded as one of the effective antigen-presenting cells, but the relationship between DCs and lymphocytes, in particular natural killer (NK) cells, remains unclear. In this study, we evaluated how DCs interact with both lymphocytes and NK cells using a coculture system. The number of lymphocytes increased significantly when cocultured with DCs (1.8-fold increase). In particular, the proliferation of NK cells was prominent. Furthermore, the coculture of DCs with lymphocytes induced a marked increase in IL-12 and IFN-gamma secretion. When contact between the DCs and lymphocytes was prevented, the secretion of both IL-12 and IFN-gamma was markedly reduced. IFN-gamma production was completely blocked by an anti-IL-12 antibody, indicating that IFN-gamma secretion was dependent on IL-12 secretion. The stimulating effect of the DCs on the proliferation of the lymphocytes was partially suppressed by anti-IL-12 antibodies, and was completely attenuated when cellular contact was prevented. Furthermore, the NK cell proliferation induced by coculture with DCs was significantly blocked by the inhibition of the interaction of either CD40-CD40L or CD28-B7 molecule. The coculture with DCs enhanced NK activity by 40%, and this was partially suppressed by anti-IL-12 antibodies and was completely blocked by the inhibition of cell-to-cell contact. These results indicate that the activation of NK cells by DCs is partially mediated by IL-12 secretion, and that direct contact between DCs and NK cells play a major role in this response.