Kuhlman P, Moy V T, Lollo B A, Brian A A
Department of Chemistry, University of California, San Diego, La Jolla 92093-0063.
J Immunol. 1991 Mar 15;146(6):1773-82.
These studies demonstrate that the murine intercellular adhesion molecule-1 (ICAM-1) performs at least two roles in enhancing T cell activation. These two roles are evident in both of our experimental systems: with ICAM-1 expressed on the surface of transfected fibroblast cells, and with purified ICAM-1 immobilized on plastic. First, as has been documented by many investigators, ICAM-1 mediates adhesion between ICAM-1- and lymphocyte function-associated Ag-1 (LFA-1)-bearing cells. This adhesive interaction occurs even in the absence of T cell stimulation, although it is increased by addition of phorbol ester and calcium ionophore. Although ICAM-1 expression does markedly increase intercellular adhesion, the increase is significantly less than the improvement ICAM-1 expression makes in the Ag-presenting ability of MHC class II-transfected fibroblast cells. We have investigated whether this difference is due to LFA-1-mediated signaling, and we present data that demonstrates that although ICAM-1 does not deliver costimulatory signals required for T cell activation, the interaction of LFA-1 with ICAM-1 does synergize with TCR-transduced signals. This synergy is observed for ICAM-1 on live and on chemically fixed accessory cells, and for purified ICAM-1 molecules, but in all cases occurs only when the ICAM-1 and the TCR ligands are on the same surface. Finally, when the ICAM-1 is present on the surface of accessory cells, it enhances T cell activation by changing the Ag dose-dependence of the T cell, but when ICAM-1 and CD3 mAb are co-immobilized, ICAM-1 increases the peak response of the T cell without affecting the dose dependence of the response.
这些研究表明，小鼠细胞间黏附分子-1（ICAM-1）在增强T细胞活化过程中至少发挥两种作用。在我们的两个实验系统中，这两种作用都很明显：一种是ICAM-1在转染的成纤维细胞表面表达，另一种是将纯化的ICAM-1固定在塑料上。首先，正如许多研究者所记录的，ICAM-1介导ICAM-1与携带淋巴细胞功能相关抗原-1（LFA-1）的细胞之间的黏附。即使在没有T细胞刺激的情况下，这种黏附相互作用也会发生，不过添加佛波酯和钙离子载体后会增强。尽管ICAM-1的表达确实会显著增加细胞间黏附，但这种增加明显小于ICAM-1表达对MHC II类转染成纤维细胞抗原呈递能力的改善。我们研究了这种差异是否是由于LFA-1介导的信号传导所致，并提供了数据表明，虽然ICAM-1不传递T细胞活化所需的共刺激信号，但LFA-1与ICAM-1的相互作用确实与TCR转导的信号协同作用。在活的和化学固定的辅助细胞上的ICAM-1以及纯化的ICAM-1分子中都观察到了这种协同作用，但在所有情况下，只有当ICAM-1和TCR配体在同一表面时才会发生。最后，当ICAM-1存在于辅助细胞表面时，它通过改变T细胞的抗原剂量依赖性来增强T细胞活化，但当ICAM-1和CD3单克隆抗体共同固定时，ICAM-1会增加T细胞的峰值反应而不影响反应的剂量依赖性。
