Differential expression and function of CD8O (B7-1) and CD86 (B7-2) on human peripheral blood monocytes
Differential expression and function of CD8O (B7-1) and CD86 (B7-2) on human peripheral blood monocytes
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DOI：
10.1046/j.1365-2567.1996.d01-785.x
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发表时间：
1996-12-01
期刊：
影响因子：
6.4
通讯作者：
Ernst, M
中科院分区：
文献类型：
--
作者：
Fleischer, J;Soeth, E;Ernst, M
CD 28与其配体的相互作用对于T细胞活化很重要。最近的研究表明，辅助细胞上至少存在两种配体，CD 80（B7-1）和CD 86（B7-2）。在这项研究中，我们证明，虽然CD 80和CD 86都在单核细胞上表达，但它们似乎具有不同的功能。新鲜分离的单核细胞表达CD 86，但为CD 80阴性。在体外培养6-8小时后，CD 80表达被弱诱导，并且通过刺激而增强。在刺激的细胞中，CD 86表达比CD 80表达更快地增强，并且在4-6小时后达到峰值水平。逆转录-聚合酶链反应研究表明，新鲜分离的单核细胞不含CD 80-mRNA。CD 80的mRNA在培养4- 6小时后被诱导，这与蛋白质的表达相匹配。使用针对这两种分子和融合蛋白CTLA 4 Ig的不同抗体的抑制研究表明，只有抗CD 8 O和CTLA 4 Ig可以部分抑制抗原特异性（结核菌素）和多克隆（抗CD 3）淋巴细胞增殖和干扰素-γ（IFN-γ）分泌的T细胞与自体单核细胞共培养。IFN-γ分泌对阻断共刺激的敏感性低于增殖。抗体BB-1不抑制增殖和细胞因子分泌，抗CD 86克隆IT2.2也不抑制增殖和细胞因子分泌。CTLA 4 Ig结合CD 80和CD 86两者，具有与测试的抗CD 80抗体相同的抑制能力。从这些发现中，我们得出结论，人单核细胞使用CD 80作为CD 28的共刺激配体，并利用其他共刺激机制，除了通过B7家族的分子介导的。
The interaction of CD28 with its ligands is important for T-cell activation. Recent studies demonstrated the existence of at least two ligands on accessory cells, CD80 (B7-1) and CD86 (B7-2). In this study we demonstrate that, although CD80 and CD86 are both expressed on monocytes, they seem to have different functions. Freshly isolated monocytes express CD86 but are CD80-negative. CD80 expression is weakly induced after 6-8 hr of in vitro culture and is enhanced by stimulation. CD86 expression is enhanced faster than CD80 expression and reaches the peak level after 4-6 hr in stimulated cells. Reverse transcription-polymerase chain reaction studies demonstrate that freshly isolated monocytes contain no CD80-mRNA. The mRNA of CD80 is induced after 4-6hr of culture, which matches with the expression of the protein. Inhibition studies using different antibodies against both molecules and the fusion protein CTLA4Ig show that only anti-CD8O and CTLA4Ig could partially inhibit antigen-specific (tuberculin) and polyclonal (anti-CD3) lymphoproliferation and interferon-gamma (IFN-gamma) secretion of T cells cocultured with autologous monocytes. IFN-gamma secretion was mon sensitive to blocking costimulation than proliferation. The antibody BB-1 did not inhibit proliferation and cytokine secretion, nor did the anti-CD86 clone IT2.2. CTLA4Ig, which binds both CD80 and CD86, has the same inhibitory capacity as the anti-CD80 antibody tested. From those findings we conclude that human monocytes use CD80 as a costimulatory ligand for CD28 and utilize other costimulatory mechanisms besides those mediated via molecules of the B7 family.