Dendritic cells from malaria-infected mice are fully functional APC

Dendritic cells from malaria-infected mice are fully functional APC
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DOI:
10.4049/jimmunol.172.1.475
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发表时间:
2004-01-01
影响因子:
4.4
通讯作者:
Avery, AC
Avery, AC
中科院分区:
医学2区
文献类型:
--
作者:
Perry, JA;Rush, A;Avery, AC

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长期以来,疟疾感染与体外T细胞反应减弱有关,最近在体内实验研究中也是如此。疟疾期间T细胞增殖反应的抑制归因于多种鼠和人系统中的巨噬细胞。然而,最近,人们的注意力集中在树突状细胞在这一现象中的作用上,一些研究表明,树突状细胞的成熟在体外被疟疾感染的E.在这里报道的研究中,我们已经检查了直接从感染小鼠中提取的树突状细胞的功能。我们发现,它们表达高水平的共刺激蛋白和II类MHC,可以激活幼稚T细胞产生IL-2有效的树突状细胞从未感染的小鼠,并支持高水平的IFN-γ的生产幼稚T细胞通过IL-12依赖性机制。来自感染小鼠的树突状细胞也支持幼稚T细胞产生更高水平的TNF-α。这些树突状细胞将寄生虫抗原呈递给疟疾特异性T细胞杂交瘤,这一发现表明树突状细胞在感染期间参与产生抗原特异性免疫。我们的发现挑战了树突状细胞功能被疟疾感染抑制的论点。
Malaria infection has long been associated with diminished T cell responses in vitro and more recently in experimental studies in vivo. Suppression of T cell-proliferative responses during malaria has been attributed to macrophages in a variety of murine and human systems. More recently, however, attention has been directed at the role of dendritic cells in this phenomenon, with several studies suggesting that maturation of dendritic cells is inhibited in vitro by the presence of malaria-infected E. In the studies reported here, we have examined the function of dendritic cells taken directly from infected mice. We found that they express high levels of costimulatory proteins and class II MHC, can activate naive T cells to produce IL-2 as efficiently as dendritic cells from uninfected mice, and support high levels of IFN-gamma production by naive T cells through an IL-12-dependent mechanism. Dendritic cells from infected mice also support higher levels of TNF-alpha production by naive T cells. These same dendritic cells present parasite Ag to a malaria-specific T cell hybridoma, a finding that demonstrates that dendritic cells participate in the generation of Ag-specific immunity during infection. Our findings challenge the contention that dendritic cell function is inhibited by malaria infection.