Influence of costimulatory molecules on immune response to Leishmania major by human cells in vitro
Influence of costimulatory molecules on immune response to Leishmania major by human cells in vitro
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DOI：
10.1128/iai.69.2.665-672.2001
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发表时间：
2001-02-01
影响因子：
3.1
通讯作者：
Titus, RG
中科院分区：
文献类型：
--
作者：
Brodskyn, CI;DeKrey, GK;Titus, RG
已经在鼠模型中确定了CD 40、CD 80和CD 86共刺激分子在抗利什曼原虫免疫应答中的重要性。在这项研究中，这些共刺激分子在人类抗利什曼原虫免疫应答中的作用进行了研究。自体巨噬细胞和外周血白细胞（PBL）从未感染利什曼原虫的供体的外周血单核细胞制备，并以各种组合与或不与硕大利什曼原虫一起培养。培养7天后，在有或无L.少校当巨噬细胞与PBL再培养7天时，检测到所有三种共刺激分子的表达。当L少校在场时。在这些培养物中，巨噬细胞上CD 80的表达增强，并且在较小程度上CD 40的表达增强。在含有巨噬细胞、PBL和L.阻断CD 40-CD 154相互作用也能显著抑制这些细胞因子的产生。少校IL-10的产生不受这些共刺激分子的阻断的影响。因此，这些数据表明：CD 30，CD 80和CD 86的表达和调节可能会显着影响人类抗利什曼原虫免疫应答。
The importance of CD40, CD80, and CD86 costimulatory molecules in anti-leishmania immune responses has been established in murine models. A role for these costimulatory molecules in human anti-leishmania immune responses was investigated in this study. Autologous macrophages and peripheral blood leukocytes (PBL) were prepared from peripheral blood mononuclear cells of leishmania-naive donors and cultured with or without Leishmania major in various combinations. After 7 days of culture, high levels of CD40 and CD86 were expressed on macrophages in the presence or absence of L. major. When macrophages were cultured for an additional 7 days with PBL, expression of all three costimulatory molecules was detected. When L, major was present. in these cultures, the expression of CD80, and to a lesser extent CD40, on macrophages was enhanced. Blockade of CD80, CD86, or both molecules tin the order of greatest effect) in cultures containing macrophages, PBL, and L. major significantly inhibited the production of gamma interferon, interleukin-5 (IL-5), and IL-12, Blockade of CD40-CD154 interactions also significantly inhibited production of these cytokines in response to L. major. Production of IL-10 was unaltered by the blockade of these costimulatory molecules. Thus, these data suggest: that CD30, CD80, and CD86 expression and regulation may significantly impact anti-leishmania immune responses in humans.