Teh H S, Teh S J
The Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Cell Immunol. 2001 Feb 1;207(2):100-9. doi: 10.1006/cimm.2000.1757.
Whether the CD28/B7 signaling pathway is essential for the negative selection of immature CD4+CD8+ (DP) thymocytes expressing self-specific alphabeta TCRs is a controversial issue. In this study we examined the role of CD28 in the deletion of thymocytes that express either the H-Y or the 2C transgenic TCR. In H-2(b) male mice that expressed the H-Y TCR, negative selection of DP H-Y TCR+ thymocytes occurred very efficiently and this deletion was unaffected by the CD28(-/-) mutation. In H-2(b) 2C mice, where the deletion of DP 2C TCR+ thymocytes occurred less efficiently, the CD28(-/-) mutation led to a higher recovery of DP thymocytes. Using an in vitro deletion assay, a requirement for the CD28 signaling pathway in the deletion of DP H-Y TCR+ thymocytes was evident at low, but not high, densities of the antigenic ligand. Similar results were also observed in an in vivo assay for the deletion of these thymocytes. Intraperitoneal administration of an anti-CD3epsilon mAb led to the intrathymic deletion of DP H-Y TCR+ thymocytes in a CD28-dependent manner at the 24-h time point. However, the CD28 dependence was less evident at the 40-h time point. These results indicate that the dependence on CD28 for the efficient deletion of self-specific thymocytes is determined by the concentration, affinity/avidity, and length of exposure to the deleting ligand.
CD28/B7信号通路对于表达自身特异性αβTCR的未成熟CD4+CD8+（DP）胸腺细胞的阴性选择是否至关重要，这是一个有争议的问题。在本研究中，我们研究了CD28在表达H-Y或2C转基因TCR的胸腺细胞缺失中的作用。在表达H-Y TCR的H-2(b)雄性小鼠中，DP H-Y TCR+胸腺细胞的阴性选择非常有效，并且这种缺失不受CD28(-/-)突变的影响。在H-2(b) 2C小鼠中，DP 2C TCR+胸腺细胞的缺失效率较低，CD28(-/-)突变导致DP胸腺细胞的回收率更高。使用体外缺失试验，在低但非高密度的抗原配体情况下，DP H-Y TCR+胸腺细胞的缺失明显需要CD28信号通路。在这些胸腺细胞缺失的体内试验中也观察到了类似结果。腹腔注射抗CD3ε单克隆抗体在24小时时间点以CD28依赖的方式导致DP H-Y TCR+胸腺细胞在胸腺内缺失。然而，在40小时时间点，CD28依赖性不太明显。这些结果表明，对CD28的依赖对于自身特异性胸腺细胞的有效缺失是由删除配体的浓度、亲和力/亲合力和暴露时间决定的。
