Abundant expression of CD40 and CD40-ligand (CD154) in paediatric Langerhans cell histiocytosis lesions
Abundant expression of CD40 and CD40-ligand (CD154) in paediatric Langerhans cell histiocytosis lesions
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DOI：
10.1016/s0959-8049(00)00296-3
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发表时间：
2000-10-01
影响因子：
8.4
通讯作者：
Claassen, E
中科院分区：
文献类型：
--
作者：
Egeler, RM;Favara, BE;Claassen, E
朗格汉斯细胞组织细胞增生症(LCH)的发病机制尚不清楚，部分原因是导致朗格汉斯样病变细胞(LCH细胞)及其相关T细胞活化的事件，以及这些细胞过度产生细胞因子的情况。CD40与活化的CD4+T细胞表达的CD40配体(CD40L)之间的相互作用是激活抗原提呈细胞(APC)和T细胞并导致APC功能上调和免疫反应启动所必需的。CD40-CD40L相互作用的作用包括增加共刺激分子和黏附分子的表达、增殖和产生促炎细胞因子和蛋白水解酶，这些都是LCH的特征。应用免疫组织化学方法，对15例儿童LCH新鲜冰冻活检组织中共刺激分子CD40和CD40L的表达进行了原位分析。LCH细胞上CD1a和T细胞上CD3双重染色鉴定产生这些分子的细胞。LCH细胞CD40和T细胞CD40L在所有15例标本中均有显著表达，无论标本来源或患者特征如何。CD40和CD40L的高表达提示CD40-CD40L黏附通路在LCH的发病机制中起关键作用。由于这种相互作用是免疫治疗的一个可接近和现实的靶点，这些发现促使人们猜测在LCH的治疗中使用CD40或CD40L的封闭抗体。(C)2000爱思唯尔科学有限公司。保留所有权利。
The pathogenesis of Langerhans cell histiocytosis (LCH) is obscure, partly because the events leading to activation of Langerhans-like lesional cells (LCH cells) and associated T cells, and the excessive cytokine production by these cells are unknown. The interaction between CD40 on antigen-presenting cells (APC) like Langerhans cells and CD40 ligand (CD40L) (CD154) expressed by activated CD4+ T cells, is essential for the activation of both the APC and the T cells and results in upregulation of APC functions and initiation of immunoreactivity. The effects of CD40-CD40L interaction include increased expression of co-stimulatory and adhesion molecules, proliferation, and production of pro-inflammatory cytokines and proteolytic enzymes, all features of LCH. Using immunohistochemistry, we analysed the irt situ presence of the co-stimulatory molecules CD40 and CD40L in 15 fresh frozen biopsies of LCH lesions in children. The cells producing these molecules were identified by double staining for CD1a on LCH cells and CD3 on T cells. Prominent expression of CD40 by LCH cells and CD40L by T cells was found in all 15 specimens regardless of the source of specimen or characteristics of the patient. The findings of high expression of CD40 and CD40L in all specimens imply a key role for the CD40-CD40L adhesion pathway in the pathogenesis of LCH. Since this interaction is an accessible and realistic target for immunotherapy, these findings prompt speculation on the use of blocking antibodies to CD40 or to CD40L in the treatment of LCH. (C) 2000 Elsevier Science Ltd. All rights reserved.