Lipopolysaccharide modulation of dendritic cells is insufficient to mature dendritic cells to generate CTLs from naive polyclonal CD8+ T cells in vitro, whereas CD40 ligation is essential
Lipopolysaccharide modulation of dendritic cells is insufficient to mature dendritic cells to generate CTLs from naive polyclonal CD8+ T cells in vitro, whereas CD40 ligation is essential
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DOI：
10.4049/jimmunol.167.11.6247
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发表时间：
2001-12-01
影响因子：
4.4
通讯作者：
Beverley, PCL
中科院分区：
文献类型：
--
作者：
Kelleher, M;Beverley, PCL
许多细胞毒性CD 8（+）T细胞应答依赖于辅助性CD 4（+）T细胞上的CD 40配体和APC上的CD 40之间的相互作用。虽然已经显示树突状细胞（DC）的CD 40触发通过增加共刺激分子的表达水平和诱导IL-12分泌使DC成熟，但是CD 40-CD 40配体相互作用允许DC驱动CTL应答的精确机制仍然未知。我们已经使用了一种体外模型，其中幼稚多克隆CD 8（+）T细胞可以被骨髓来源的DC激活，以研究负责这种CD 40依赖性CTL产生的因素。用激动性抗CD 40 mAb（aCD 40）调节的DC能够产生Ag特异性CTL应答，而用单独的微生物刺激物LPS调节的DC不能。我们比较了抗原呈递能力，共刺激分子的水平，和释放的细胞因子和趋化因子的DC与aCD 40的LPS调制的DC。没有一个分析的因素能解释抗CD 40成熟DC驱动CTL的独特能力，但该模型为进一步研究提供了一个简化的系统。尽管我们试图使用无LPS系统进行这些研究，但我们不能排除极低水平的内毒素（< 20 pg/ml）可能与CD 40连接在CTL产生中协同作用的可能性。
Many cytotoxic CD8(+) T cell responses are dependent on the interactions between CD40 ligand on the helper CD4(+) T cell and CD40 on the APC. Although CD40 triggering of dendritic cells (DC) has been shown to mature the DC by increasing the level of expression of costimulatory molecules and inducing IL-12 secretion, the precise mechanisms by which CD40-CD40 ligand interactions allow DC to drive CTL responses remain unknown. We have used an in vitro model in which naive polyclonal CD8(+) T cells can be activated by bone marrow-derived DC to investigate factor(s) that are responsible for this CD40-dependent generation of CTLs. DC modulated with agonistic anti-CD40 mAb (aCD40) are able to generate Ag-specific CTL responses while DC modulated with the microbial stimulus LPS alone do not. We compared the Ag-presenting capacity, levels of costimulatory molecules, and release of cytokines and chemokines of DC modulated with aCD40 to that of DC modulated by LPS. None of the factors assayed account for the unique capacity of anti-CD40-matured DC to drive CTL but this model provides a simplified system for further investigation. Although we attempted to use an LPS-free system for these studies, we are unable to rule out the possibility that very low levels of endotoxin (< 20 pg/ml) may synergize with CD40 ligation in the generation of CTLs.