MECHANISM OF DIFFERENTIATION OF FUNCTION OF CD80 & CD86

两种共刺激分子（CD80和CD86）在专业APC膜上表达的生物学原理尚不清楚。许多结果表明，这两种分子向t细胞提供等效的共刺激信号。在体内和体外模型中也描述了CD80和CD86在不同t细胞亚群激活中的不同作用。我们发表的数据以及其他结果表明，CD86，而不是CD80，在小鼠DNA接种期间刺激细胞免疫反应。重要的问题是为什么接种疫苗后t细胞反应的增强需要CD86，而不需要CD80 ？基于我们的研究结果，我们提出了几种解释疫苗接种后这些细胞反应的机制。基于我们的研究结果，我们提出了几种机制来解释CD80和CD86分子之间的这些功能差异。首先，MHC I类和CD86的表达，而不是CD80与免疫原的表达，可能诱导对产生免疫应答至关重要的免疫能力细胞的局部侵袭。其次，CD80和CD86可能激活不同的t细胞亚群。第三，CD80和CD86分子触发受体可能向t细胞提供不同的信号。最后，连接APC表面的CD86，而不是CD80，可以向这些细胞提供重要的信号，进而诱导产生某些分子，如细胞因子/淋巴因子/趋化因子，这些分子对T细胞活化很重要。为了评估这些假设，我们建议使用DNA免疫作为模型系统来研究以下内容：MHC I类阳性或阴性肌肉组织微环境中CD80和CD86表达的差异效应（即免疫能力细胞在DNA接种部位的侵袭）。2）. 免疫原和表达CD80/CD86的质粒共同免疫后，不同亚群的CTL （CD4+或C8+）和T辅助细胞（Th1或Th2）的活化。3）. 人CD86分子功能区/s与编码免疫原和不同CD80/CD86突变分子的DNA共同免疫后参与细胞免疫应答增强。4)专业APC产生的共刺激分子和细胞因子对DNA接种后t细胞活化的协同作用。5)。CD86与CD80结扎后基因在肌肉细胞和专业APC上的差异表达。

The biological rationale for the expression of two co-stimulatory molecules (CD80 and CD86) on the membrane of professional APC is not clear. Many results demonstrate that both molecules provide equivalent co-stimulatory signals to T-cells. Different roles for CD80 and CD86 in the activation of distinct subpopulations of T-cells have also been described in both in vivo and in vitro models. Our published data along with other results indicate that CD86, but not CD80, stimulates cellular immune responses during DNA vaccination of mice. The important question is why CD86, but not CD80 is required for augmentation of T-cell response after vaccination? Based on our results we suggest several mechanisms to explain these cell responses after vaccination? Based on our results we suggest several mechanisms to explain these functional differences between CD80 and CD86 molecules. First, expression of MHC class I and CD86, but not CD80 along with immunogen may induce local invasion of immunocompetent cells crucial for generation of immune responses. Second, CD80 and CD86 may activate different subpopulations of T-cells. Third, the triggering of receptors with CD80 and CD86 molecules may supply different signals to T-cells. Finally, the ligation of CD86, but not CD80 on the surface of APC could provide important signal to these cells and in turn induce production of certain molecules such as cytokines/lymphokines/chemokines, which are important for T cell activation. To evaluate these hypotheses we propose using DNA immunization as a model system to investigate the following: 1.) The differential effects of CD80 and CD86 expression in the microenvironment of MHC class I positive or negative muscle tissues (i.e. the invasion of immunocompetent cells at the site of DNA inoculation). 2). The activation of different subsets of CTL (CD4+ or C8+) and T helper cells (Th1 or Th2) after co-immunization with immunogen and CD80/CD86 expressing plasmids. 3). The functional region/s of human CD86 molecule involved in enhancement of cellular immune responses after co-immunization with DNA encoding immunogen and different CD80/CD86 mutant molecules. 4) The synergistic effect of co- stimulatory molecules and cytokines produced by professional APC, on T-cell activation after DNA vaccination. 5). The differential expression of genes after ligation of CD86 versus CD80 on muscle cells and professional APC.