Regulation of the class II MHC pathway in primary human monocytes by granulocyte-macrophage colony-stimulating factor
Regulation of the class II MHC pathway in primary human monocytes by granulocyte-macrophage colony-stimulating factor
复制标题
DOI：
10.4049/jimmunol.171.5.2374
复制
发表时间：
2003-09-01
影响因子：
4.4
通讯作者：
Mellins, ED
中科院分区：
文献类型：
--
作者：
Hornell, TMC;Beresford, GW;Mellins, ED
GM-CSF刺激造血祖细胞的生长和分化，也影响成熟细胞的功能。这些影响导致使用GM-CSF作为疫苗佐剂，并取得了良好的结果；然而，转基因csf介导的免疫增强机制尚不完全清楚。在这项研究中，我们研究了GM-CSF的免疫刺激作用部分是由于对II类MHC Ag呈递的影响。我们发现，在处理24-48小时的原代人单核细胞中，GM-CSF增加了表面II类MHC的表达，并降低了与表面II类分子结合的不变链衍生肽CLIP的相对水平。GM-CSF也增加共刺激分子CD86和CD40的表达，但不增加分化标志物CD1a或CD16的表达。此外，gm - csf处理的单核细胞在混合白细胞反应中是更好的刺激物。II类通路的进一步分析显示，GM-CSF增加HLA-DR、DM和doα的总蛋白和RNA水平。II类反激活因子（CIITA） I型和III型的表达，而不是IV型，转录物对GM-CSF的反应增加。此外，GM-CSF增加了与DR启动子相关的CIITA的数量。因此，我们的数据表明GM-CSF的促炎作用部分是通过诱导CHTA增加II类MHC通路中关键分子的表达来介导的。
GM-CSF stimulates the growth and differentiation of hematopoietic progenitors and also affects mature cell function. These effects have led to the use of GM-CSF as a vaccine adjuvant with promising results; however, the mechanisms underlying GM-CSF-mediated immune potentiation are incompletely understood. In this study, we investigated the hypothesis that the immune stimulatory role of GM-CSF is in part due to effects on class II MHC Ag presentation. We find that, in primary human monocytes treated for 24-48 h, GM-CSF increases surface class II MHC expression and decreases the relative level of the invariant chain-derived peptide, CLIP, bound to surface class II molecules. GM-CSF also increases expression of the costimulatory molecules CD86 and CD40, but not the differentiation marker CD1a or CD16. Furthermore, GM-CSF-treated monocytes are-better stimulators in a mixed leukocyte reaction. Additional analyses of the class II pathway revealed that GM-CSF increases total protein and RNA levels of HLA-DR, DM, and DOalpha. Expression of class II transactivator (CIITA) types I and III, but not IV, transcripts increases in response to GM-CSF. Furthermore, GM-CSF increases the amount of CIITA associated with the DR promoter. Thus, our data argue that the proinflammatory role of GM-CSF is mediated in part through increased expression of key molecules involved in the class II MHC pathway via induction of CHTA.