Accelerated in vitro differentiation of blood monocytes into dendritic cells in human sepsis
Accelerated in vitro differentiation of blood monocytes into dendritic cells in human sepsis
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DOI：
10.1111/j.1365-2249.2006.03287.x
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发表时间：
2007-03-01
影响因子：
4.6
通讯作者：
Haziot, A.
中科院分区：
文献类型：
--
作者：
Faivre, V.;Lukaszewicz, A. -C.;Haziot, A.
脓毒症诱导的免疫抑制以感染易感性和单核细胞早期失活为特征。由于单核细胞是树突状细胞（DC）的前体细胞，其分化为DC的改变可能导致败血症患者免疫应答缺陷。因此，我们研究了腹膜炎手术患者单核细胞体外分化为功能性DC的能力。从20名患者手术后立即（D 0），在第1周和第3-4周收集的单核细胞和11名对照供体分化成未成熟的DC。我们确定了单核细胞和衍生DC的表型，并分析了DC对微生物产物的反应能力和在混合白细胞反应（MLR）中引起T细胞反应的能力。我们发现，虽然脓毒症患者的单核细胞被灭活，对脂多糖（LPS）和肽聚糖的反应降低，人类白细胞抗原D相关（HLA-DR）表达降低，但它们表达共刺激分子CD 80，CD 40和CCR 7。在D 0和第1周从患者收集的单核细胞更快地分化为DC，早期CD 14表达丧失。HLA-DR的表达在培养物中显著增加以达到对照水平，DC对LPS和肽聚糖的反应也是如此。然而，尽管患者和对照组未成熟DC在MLR中诱导T细胞增殖的能力相似，但患者来源的DC的成熟并不增加T细胞应答。这些结果表明，尽管功能失活，但来自脓毒症患者的循环单核细胞表达活化和/或分化的标志物，并迅速分化为表型正常的DC。然而，这些DC在成熟后未能增加其T细胞活化能力。
Sepsis-induced immune depression is characterized by infection susceptibility and monocyte early deactivation. Because monocytes are precursors for dendritic cells (DC), alterations in their differentiation into DC may contribute to defective immune responses in septic patients. We therefore investigated the ability of monocytes to differentiate into functional DC in vitro in patients undergoing surgery for peritonitis. Monocytes from 20 patients collected immediately after surgery (D0), at week 1 and at weeks 3-4 and from 11 control donors were differentiated into immature DC. We determined the phenotype of monocytes and derived DC, and analysed the ability of DC to respond to microbial products and to elicit T cell responses in a mixed leucocyte reaction (MLR). We show that, although monocytes from septic patients were deactivated with decreased responses to lipopolysaccharide (LPS) and peptidoglycan and low human leucocyte antigen D-related (HLA-DR) expression, they expressed the co-stimulatory molecule CD80, CD40 and CCR7. Monocytes collected from patients at D0 and week 1 differentiated faster into DC with early loss of CD14 expression. Expression of HLA-DR increased dramatically in culture to reach control levels, as did responses of DC to LPS and peptidoglycan. However, although patient and control immature DC had similar abilities to induce T cell proliferation in MLR, maturation of DC derived from patients did not increase T cell responses. These results show that circulating monocytes from septic patients express markers of activation and/or differentiation despite functional deactivation, and differentiate rapidly into phenotypically normal DC. These DC fail, however, to increase their T cell activation abilities upon maturation.