Nickoloff B J, Mitra R S, Lee K, Turka L A, Green J, Thompson C, Shimizu Y
Department of Pathology, University of Michigan, Ann Arbor.
Am J Pathol. 1993 Apr;142(4):1029-40.
The process for optimal T-cell activation requires not only engagement of the T-cell receptor/CD3 complex, but also the delivery of additional co-stimulatory signals that synergize with the primary response mediated through the T-cell receptor. Thus, the regulated expression of ligands for such co-stimulatory molecules can be critical in determining whether a cell can effectively activate T cells following the presentation of a foreign antigen. The CD28 antigen has recently been shown to mediate such co-stimulatory signals by interacting with the B7/BB-1 molecule expressed on activated B cells and monocytes. We show in this study that activated keratinocytes, both in vitro and in vivo display a discordance in expression between B7 and BB-1 based on differential monoclonal antibody (MAb) reactivity. Activated keratinocytes in vitro, as well as psoriatic keratinocytes and epithelial cells in the thymus, are reactive with the BB-1 MAb but not anti-B7 MAbs. These BB-1 positive cells fail to express detectable B7 messenger RNA by Northern blot analysis. Furthermore, keratinocytes bind specifically to CD28-transfected COS7 cells, and this binding is inhibited by anti-CD28 and anti-BB-1 but not B7 MAbs. These studies suggest: 1) that the MAb against BB-1 binds a functional epitope on a molecule distinct from B7 as detected on activated keratinocytes in vitro and in vivo and 2) that keratinocytes in skin and epithelial cells in thymus can express cell-surface molecules that might mediate T-cell co-stimulation via CD28.
最佳T细胞激活过程不仅需要T细胞受体/CD3复合物的结合,还需要传递额外的共刺激信号,这些信号与通过T细胞受体介导的主要反应协同作用。因此,此类共刺激分子配体的调控表达对于确定细胞在呈递外来抗原后是否能有效激活T细胞可能至关重要。最近研究表明,CD28抗原通过与活化B细胞和单核细胞上表达的B7/BB-1分子相互作用来介导此类共刺激信号。我们在本研究中发现,活化的角质形成细胞在体外和体内基于不同的单克隆抗体(MAb)反应性,在B7和BB-1的表达上存在不一致。体外活化的角质形成细胞以及胸腺中的银屑病角质形成细胞和上皮细胞与BB-1 MAb反应,但不与抗B7 MAb反应。通过Northern印迹分析,这些BB-1阳性细胞未能表达可检测到的B7信使RNA。此外,角质形成细胞特异性结合转染了CD28的COS7细胞,这种结合被抗CD28和抗BB-1 MAb抑制,但不被B7 MAb抑制。这些研究表明:1)抗BB-1 MAb在体外和体内活化的角质形成细胞上检测到的与B7不同的分子上结合一个功能性表位;2)皮肤中的角质形成细胞和胸腺中的上皮细胞可以表达可能通过CD28介导T细胞共刺激的细胞表面分子。