Activation of human dendritic cells through CD40 cross-linking.
Activation of human dendritic cells through CD40 cross-linking.
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DOI：
10.1084/jem.180.4.1263
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发表时间：
1994-10-01
期刊：
影响因子：
--
通讯作者：
Banchereau J
中科院分区：
文献类型：
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作者：
Caux C;Massacrier C;Vanbervliet B;Dubois B;Van Kooten C;Durand I;Banchereau J
树突状细胞（Dendritic cells，DC）是参与T细胞启动的专职抗原提呈细胞（antigen presenting cells，APC），其表达的CD 40分子在B细胞的生长、分化以及单核细胞的活化中起关键作用。在此，我们证明了通过用粒细胞/巨噬细胞集落刺激和肿瘤坏死因子α（TNF-α）培养脐带血CD 34+祖细胞产生的树突状朗格汉斯细胞（D-Lc）以高于在B细胞上发现的密度表达功能性CD 40。在CD 40配体（CD 40 L）转染的L细胞上培养D-Lc允许D-Lc存活，因为4天后回收了50 +/- 15%的接种细胞，而对照L细胞仅存活5%。CD 40活化诱导了重要的形态学变化，细胞质含量减少，树突发育显著增加，表型改变。特别是，CD 40触发诱导维持高水平的主要组织相容性复合物II类抗原和上调辅助分子，如CD 58，CD 80（B7-1）和CD 86（B7-2）。CD 40的参与似乎也开启了D-Lc的成熟，如CD 25的上调所示，CD 25是一种通常在次级淋巴器官的交错树突状细胞上表达的分子。最后，CD 40活化的D-Lc分泌有限的一组细胞因子（TNF-α、IL-8和巨噬细胞炎性蛋白1 α [MIP-1 α]），而类似的活化诱导淘析的单核细胞分泌IL-1 α、IL-1 β、IL-6、IL-8、IL-10、TNF-α和MIP-1 α。由于D-Lc活化的T细胞上调CD 40 L，因此本文中用稳定表达CD 40 L的成纤维细胞系观察到的D-Lc的CD 40活化可能模拟树突细胞和T细胞之间的生理相互作用。
Dendritic cells, the professional antigen-presenting cells (APC) involved in T cell priming, express CD40, a molecule which triggering plays a key role in B cell growth and differentiation as well as monocyte activation. Herein we demonstrate that dendritic Langerhans cells (D-Lc) generated by culturing cord blood CD34+ progenitor cells with granulocyte/macrophage colony-stimulating and tumor necrosis factor alpha (TNF-alpha) express functional CD40 at a density higher than that found on B cells. Culturing D-Lc on CD40-ligand (CD40L) transfected L cells allowed D-Lc survival as 50 +/- 15% of seeded cells were recovered after 4 d while only 5% survived over control L cells. CD40 activation induced important morphological changes with a reduction of cytoplasmic content and a remarkable increase of dendrite development as well as an altered phenotype. In particular, CD40 triggering induced maintenance of high levels of major histocompatibility complex class II antigens and upregulation of accessory molecules such as CD58, CD80 (B7-1) and CD86 (B7-2). CD40 engagement also seems to turn on D-Lc maturation as illustrated by upregulation of CD25, a molecule usually expressed on interdigitating dendritic cells of secondary lymphoid organs. Finally, CD40 activated D- Lc secreted a limited set of cytokines (TNF-alpha, IL-8, and macrophage inflammatory protein 1 alpha [MIP-1 alpha]) whereas a similar activation induced elutriated monocytes to secrete IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, TNF-alpha, and MIP-1 alpha. As D-Lc activated T cells upregulated CD40L, it is likely that CD40 activation of D-Lc observed herein with a fibroblast cell line stably expressing CD40L, mimics physiological interactions between dendritic cells and T cells.