van Dinther-Janssen A C, Kraal G, van Soesbergen R M, Scheper R J, Meijer C J
Department of Pathology, Free University and Slotervaart Hospital, Amsterdam, The Netherlands.
J Rheumatol. 1994 Nov;21(11):1998-2004.
It has previously been shown that the adhesion of lymphocytes to microvascular endothelium mediates lymphocyte extravasation within inflamed synovium. After passing the endothelial barrier, binding of lymphocytes to matrix proteins and synovial lining cells may further lead to synovial membrane hyperplasia and subsequent cartilage destruction. Thus, we have explored the molecular basis of T cell-synovial lining cell interaction in the synovial membrane of patients with rheumatoid arthritis (RA).
Using an immunohistochemical staining technique and an in vitro frozen section assay we studied the expression and the role of several adhesion molecules in T lymphocyte-synovial lining cell interaction in the inflamed synovial membrane.
In RA the macrophage-like (type A) synovial lining cells express high levels of intercellular adhesion molecule 1 [ICAM-1 (CD54)], whereas the fibroblast-like (type B) synovial lining cells predominantly express vascular cell adhesion molecule 1 (VCAM-1), in addition to moderate levels of ICAM-1. Both cell types express low levels of fibronectin. Unstimulated and anti-CD3 stimulated peripheral blood T cells bear the respective ligands lymphocyte function associated antigen 1 [LFA-1 (CD18/11a)], and very late antigen 4 and 5 [VLA-4 (CD29/49d) and VLA-5 (CD29/49e)]. T lymphocytes predominantly bound to type B synovial lining cells. Inhibition studies with monoclonal antibodies revealed that this binding involves the VLA-4/VCAM-1 and VLA-5/fibronectin (FN), but not the VLA-4/CS1 pathway. LFA-1 is also involved in this interaction via its ligand ICAM-1.
These results show that the molecular basis of T lymphocyte binding to rheumatoid synovial lining cells is different from that described for T lymphocyte binding to synovial membrane vascular endothelium which involves the VLA-4/VCAM-1 and VLA-4/CS-1 pathways, but not the LFA-1/ICAM-1 pathway.
先前的研究表明，淋巴细胞与微血管内皮的黏附介导了淋巴细胞在炎症滑膜内的渗出。穿过内皮屏障后，淋巴细胞与基质蛋白和滑膜衬里细胞的结合可能进一步导致滑膜增生及随后的软骨破坏。因此，我们探讨了类风湿关节炎（RA）患者滑膜中T细胞与滑膜衬里细胞相互作用的分子基础。
我们使用免疫组织化学染色技术和体外冰冻切片试验，研究了几种黏附分子在炎症滑膜中T淋巴细胞与滑膜衬里细胞相互作用中的表达及作用。
在RA中，巨噬细胞样（A型）滑膜衬里细胞表达高水平的细胞间黏附分子1 [ICAM-1（CD54）]，而成纤维细胞样（B型）滑膜衬里细胞除了表达中等水平的ICAM-1外，主要表达血管细胞黏附分子1（VCAM-1）。两种细胞类型均表达低水平的纤连蛋白。未刺激和抗CD3刺激的外周血T细胞分别携带各自的配体淋巴细胞功能相关抗原1 [LFA-1（CD18/11a）]，以及极晚期抗原4和5 [VLA-4（CD29/49d）和VLA-5（CD29/49e）]。T淋巴细胞主要与B型滑膜衬里细胞结合。单克隆抗体抑制研究表明，这种结合涉及VLA-4/VCAM-1和VLA-5/纤连蛋白（FN），但不涉及VLA-4/CS1途径。LFA-1也通过其配体ICAM-1参与这种相互作用。
这些结果表明，T淋巴细胞与类风湿滑膜衬里细胞结合的分子基础不同于T淋巴细胞与滑膜血管内皮结合的情况，后者涉及VLA-4/VCAM-1和VLA-4/CS-1途径，但不涉及LFA-1/ICAM-1途径。
