Dendritic cells take up and present antigens from viable and apoptotic polymorphonuclear leukocytes.

Dendritic cells take up and present antigens from viable and apoptotic polymorphonuclear leukocytes.
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DOI:
10.1371/journal.pone.0029300
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Melero I
Melero I
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Alfaro C;Suarez N;Oñate C;Perez-Gracia JL;Martinez-Forero I;Hervas-Stubbs S;Rodriguez I;Perez G;Bolaños E;Palazon A;Sanmamed MF;Morales-Kastresana A;Gonzalez A;Melero I

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树突状细胞(DC)具有将来自其他细胞类型的抗原交叉呈递给同源T细胞的能力。由于被白细胞介素-8(IL-8)(例如由肿瘤细胞或感染的组织产生的白细胞介素-8)共同吸引,DC准备好与多形核白细胞(PMN)相遇。人单核细胞来源的和小鼠骨髓来源的DC可以容易地内化活的或UV照射的PMN。这种内化在4°C下被废除,并被抗CD 18 mAb部分抑制。在小鼠中,具有内化的含有电穿孔的卵清蛋白(OVA)蛋白的PMN的DC能够将抗原交叉呈递给CD 8(OT-1)和CD 4(OT-2)TCR转基因T细胞。此外,在人类中,肿瘤细胞碎片被PMN内化,并且肿瘤细胞材料随后可以通过DC从免疫磁性再分离的PMN中摄取。重要的是,如果人类中性粒细胞内吞了细菌,它们就能够触发DC的成熟程序。此外,当小鼠PMNs与E.大肠杆菌在其内部与DC共注射在足垫中,许多负载有来自PMNs的荧光物质的DC到达引流淋巴结。使用CT 26(H-2d)小鼠肿瘤细胞,观察到如果肿瘤细胞细胞内装载有OVA蛋白并经UV照射,则它们成为H-2d PMN的吞噬猎物。如果这种不能将抗原呈递给OT-1 T细胞的PMN被免疫磁性地重新分离并被H-2b DC吞噬,则这种DC将OVA抗原决定簇有效地交叉呈递给OT-1 T细胞。当将负载OVA的PMN(H-2d)与自体DC(H-2b)共注射到小鼠的足垫中时,在引流淋巴结处也发生过继转移的OT-1淋巴细胞的交叉呈递。总之,我们的研究结果表明,抗原吞噬短寿命的中性粒细胞可以反过来内化和生产交叉提出的DC。
Dendritic cells (DC) are endowed with the ability to cross-present antigens from other cell types to cognate T cells. DC are poised to meet polymorphonuclear leukocytes (PMNs) as a result of being co-attracted by interleukin-8 (IL-8), for instance as produced by tumor cells or infected tissue. Human monocyte-derived and mouse bone marrow-derived DC can readily internalize viable or UV-irradiated PMNs. Such internalization was abrogated at 4°C and partly inhibited by anti-CD18 mAb. In mice, DC which had internalized PMNs containing electroporated ovalbumin (OVA) protein, were able to cross-present the antigen to CD8 (OT-1) and CD4 (OT-2) TCR-transgenic T cells. Moreover, in humans, tumor cell debris is internalized by PMNs and the tumor-cell material can be subsequently taken up from the immunomagnetically re-isolated PMNs by DC. Importantly, if human neutrophils had endocytosed bacteria, they were able to trigger the maturation program of the DC. Moreover, when mouse PMNs with E. coli in their interior are co-injected in the foot pad with DC, many DC loaded with fluorescent material from the PMNs reach draining lymph nodes. Using CT26 (H-2d) mouse tumor cells, it was observed that if tumor cells are intracellularly loaded with OVA protein and UV-irradiated, they become phagocytic prey of H-2d PMNs. If such PMNs, that cannot present antigens to OT-1 T cells, are immunomagnetically re-isolated and phagocytosed by H-2b DC, such DC productively cross-present OVA antigen determinants to OT-1 T cells. Cross-presentation to adoptively transferred OT-1 lymphocytes at draining lymph nodes also take place when OVA-loaded PMNs (H-2d) are coinjected in the footpad of mice with autologous DC (H-2b). In summary, our results indicate that antigens phagocytosed by short-lived PMNs can be in turn internalized and productively cross-presented by DC.
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