Measles virus infects human dendritic cells and blocks their allostimulatory properties for CD4(+) T cells
Measles virus infects human dendritic cells and blocks their allostimulatory properties for CD4(+) T cells
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DOI：
10.1084/jem.186.6.801
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发表时间：
1997-09-15
影响因子：
15.3
通讯作者：
Kaiserlian, D
中科院分区：
文献类型：
--
作者：
Grosjean, I;Caux, C;Kaiserlian, D
麻疹引起严重的免疫抑制，这是造成继发感染引起的高发病率和死亡率的原因。树突状细胞（DC）是启动原发性免疫应答所需的专职抗原呈递细胞。为了确定麻疹病毒（MV）感染DC是否可能在病毒诱导的细胞介导的免疫抑制中发挥作用，我们检测了来源于脐带血CD 34（+）祖细胞和分离自人表皮的朗格汉斯细胞的CD 1a（+）DC支持MV复制的能力。在这里，我们表明，培养的CD 1a（+）DC和表皮朗格汉斯细胞可以在体外感染的疫苗和野生型MV株。用MV感染DC在24-48 h内导致细胞-细胞融合、血凝素的细胞表面表达和与感染性病毒产生相关的病毒出芽。早在混合白细胞反应（MLR）第2天，DC的MV感染就完全消除了细胞刺激幼稚同种异体CD 4（+）T细胞增殖的能力（即，在DC感染的第4天）。甘露糖受体介导的内吞作用和活性研究表明，DC刺激功能的丧失不能归因于DC的死亡或凋亡。这种DC刺激功能的完全丧失需要在DC中进行病毒复制，因为来自MV感染的DC的紫外线（UV）灭活的MV或UV处理的上清液不改变DC的同种异体刺激能力。少至10 MV感染的DC可阻断10（4）未感染DC的刺激功能。更重要的是，MV感染的DC，其中感染性病毒的产生被UV处理或多聚甲醛固定阻断，在转移到未感染的DC-T培养物时积极抑制同种异体MLR。因此，导致DC的同种异体刺激功能丧失的机制包括病毒释放和MV感染的DC介导的主动抑制，独立于病毒产生。这些数据表明，DC携带MV可能有助于病毒传播到次级淋巴器官，DC中的MV复制可能在麻疹期间观察到的一般免疫抑制中发挥核心作用。
Measles causes a profound immune suppression which is responsible for the high morbidity and mortality induced by secondary infections. Dendritic cells (DC) are professional antigen-presenting cells required for initiation of primary immune responses. To determine whether infection of DC by measles virus (MV) may play a role in virus-induced suppression of cell-mediated immunity, we examined the ability of CD1a(+) DC derived from cord blood CD34(+) progenitors and Langerhans cells isolated from human epidermis to support MV replication. Here we show that both cultured CD1a(+) DC and epidermal Langerhans cells can be infected in vitro by both vaccine and wild type strains of MV. DC infection with MV resulted within 24-48 h in cell-cell fusion, cell surface expression of hemagglutinin, and virus budding associated with production of infectious virus. MV infection of DC completely abrogated the ability of the cells to stimulate the proliferation of naive allogeneic CD4(+) T cell as early as day 2 of mixed leukocyte reaction (MLR) (i.e., on day 4 of DC infection). Mannose receptor-mediated endocytosis and viability studies indicated that the loss of DC stimulatory function could not be attributed to the death or apoptosis of DC. This total loss of DC stimulatory function required viral replication in the DC since ultraviolet (UV)-inactivated MV or UV-treated supernatant from MV-infected DC did not alter the allostimulatory capacity of DC. As few as 10 MV-infected DC could block the stimulatory function of 10(4) uninfected DC. More importantly, MV-infected DC, in which production of infectious virus was blocked by UV treatment or paraformaldehyde fixation, actively suppressed allogeneic MLR upon transfer ro uninfected DC-T-cultures. Thus, the mechanisms which contribute to the loss of the allostimulatory function of DC include both virus release and active suppression mediated by MV-infected DC, independent of virus production. These data suggest that carriage of MV by DC may facilitate virus spreading to secondary lymphoid organs and that MV replication in DC may play a central role in the general immune suppression observed during measles.