ACTIVATION OF HUMAN PERIPHERAL-BLOOD DENDRITIC CELLS INDUCES THE CD86 COSTIMULATORY MOLECULE
ACTIVATION OF HUMAN PERIPHERAL-BLOOD DENDRITIC CELLS INDUCES THE CD86 COSTIMULATORY MOLECULE
复制标题
DOI：
10.1002/eji.1830250739
复制
发表时间：
1995-07-01
影响因子：
5.4
通讯作者：
HART, DNJ
中科院分区：
文献类型：
--
作者：
MCLELLAN, AD;STARLING, GC;HART, DNJ
最大的T淋巴细胞反应需要主要组织相容性复合体分子呈递抗原和传递一个或多个共刺激信号。T淋巴细胞表面CD28分子与其抗原提呈细胞(APC)上的配体相互作用，启动了诱导T淋巴细胞增殖和细胞因子分泌的关键共刺激途径。树突状细胞(DC)是主要的T淋巴细胞反应的有效APC，因此，DC上潜在的CD28/CTLA-4配体具有特殊的功能相关性。本实验检测了CD28/CTLA-4配体B7.1(CD80)和B7.2(CD86)在人外周血树突状细胞上的表达和功能。免疫耗竭直接分离的静止期DC细胞缺乏CD80的细胞膜表达，在逆转录-聚合酶链式反应中检测到CD86的表达，但未检测到CD80的表达。相反，体外分离的低密度DC强烈表达CD86表面蛋白，但表达有限的CD80或不表达CD80，尽管检测到这两种分子的mRNA。直接分离DC短期培养可上调CD80和CD86的表达。对CD28/CTLA-4配体诱导动力学的分析表明，CD86在8h内出现，而CD80在培养24 h后首次检测到。CD28/CTLA-4配体上调DC在T淋巴细胞相互作用中的功能重要性通过CTLA-4Ig和CD86单抗(而不是CD80单抗)阻止最初CD80和CD86阴性的DC刺激的同种异体混合淋巴细胞反应的能力来证明。这些结果表明，CD86是最早的和功能上最主要的共刺激CD28/CTLA-4的DC配体。
Maximal T lymphocyte responses require presentation of antigen by major histocompatibility complex molecules and delivery of one or more co-stimulatory signals. Interaction of the CD28 molecule on T lymphocytes with its ligands on antigen-presenting cells (APC) initiates a critical co-stimulatory pathway inducing T lymphocyte proliferation and cytokine secretion. Dendritic cells (DC) are potent APC for a primary T lymphocyte response and potential CD28/CTLA-4 Ligands on DC are, therefore, of particular functional relevance. In these experiments, the expression and function of the CD28/CTLA-4 ligands B7.1 (CD80) and B7.2 (CD86) were examined on human blood DC. Resting DC populations directly isolated by immunodepletion of lineage marker-positive cells lacked cell membrane expression of CD80 and expressed little or no CD86, although CD86, but not CD80 mRNA was detected by reverse transcription-polymerase chain reaction analysis. In contrast, low-density DC isolated after culture ia vitro strongly expressed CD86 surface protein, but expressed limited or no CD80, although mRNA for both molecules were detected. Short-term culture of directly isolated DC up-regulated both CD80 and CD86 expression. Analysis of the kinetics of CD28/CTLA-4 ligand induction showed that surface CD86 was present within 8 h, whereas CD80 antigen was first detected after 24 h of culture. The functional importance of CD28/CTLA-4 ligand up-regulation on DC during T lymphocyte interactions was demonstrated by the ability of both CTLA-4Ig and CD86 monoclonal antibodies (mAb), but not CD80 mAb, to block an allogeneic mixed lymphocyte reaction stimulated by DC populations initially negative for CD80 and CD86. These results demonstrate that CD86 is both the earliest and functionally the predominant co-stimulatory CD28/CTLA-4 ligand on DC.