通过OX40的NKT细胞-浆细胞样树突状细胞协作以组织特异性方式控制病毒感染。
NKT cell-plasmacytoid dendritic cell cooperation via OX40 controls viral infection in a tissue-specific manner.
作者信息
Diana Julien, Griseri Thibault, Lagaye Sylvie, Beaudoin Lucie, Autrusseau Elodie, Gautron Anne-Sophie, Tomkiewicz Céline, Herbelin André, Barouki Robert, von Herrath Matthias, Dalod Marc, Lehuen Agnès
机构信息
Institut National de la Santé et de la Recherche Médicale U561, Hôpital Cochin-St Vincent de Paul, Paris, France.
出版信息
Immunity. 2009 Feb 20;30(2):289-99. doi: 10.1016/j.immuni.2008.12.017. Epub 2009 Feb 12.
Invariant natural killer T (iNKT) cells promote immune responses to various pathogens, but exactly how iNKT cells control antiviral responses is unclear. Here, we showed that iNKT cells induced tissue-specific antiviral effects in mice infected by lymphocytic choriomeningitis virus (LCMV). Indeed, iNKT cells inhibited viral replication in the pancreas and liver but not in the spleen. In the pancreas, iNKT cells expressed the OX40 molecule and promoted type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs) through OX40-OX40 ligand interaction. Subsequently, this iNKT cell-pDC cooperation attenuated the antiviral adaptive immune response in the pancreas but not in the spleen. The dampening of pancreatic anti-LCMV CD8(+) T cell response prevented tissue damage in transgenic mice expressing LCMV protein in islet beta cells. Thus, this study identifies pDCs as an essential partner of iNKT cells for mounting an efficient, nondeleterious antiviral response in peripheral tissue.
不变自然杀伤T（iNKT）细胞可促进针对各种病原体的免疫反应，但iNKT细胞究竟如何控制抗病毒反应尚不清楚。在此，我们表明iNKT细胞在感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）的小鼠中诱导组织特异性抗病毒效应。事实上，iNKT细胞抑制胰腺和肝脏中的病毒复制，但不抑制脾脏中的病毒复制。在胰腺中，iNKT细胞表达OX40分子，并通过OX40-OX40配体相互作用促进浆细胞样树突状细胞（pDC）产生I型干扰素（IFN）。随后，这种iNKT细胞-pDC合作减弱了胰腺而非脾脏中的抗病毒适应性免疫反应。胰腺抗LCMV CD8(+) T细胞反应的减弱防止了在胰岛β细胞中表达LCMV蛋白的转基因小鼠的组织损伤。因此，本研究确定pDC是iNKT细胞在周围组织中发起有效、无害的抗病毒反应的重要伙伴。
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