Rodriguez R M, Pitzalis C, Kingsley G H, Henderson E, Humphries M J, Panayi G S
Division of Medicine, United Medical School, London, UK.
Clin Exp Immunol. 1992 Sep;89(3):439-45. doi: 10.1111/j.1365-2249.1992.tb06977.x.
The accumulation of T cells within the joint is responsible for the perpetuation of synovitis. This process is partly regulated by selective binding to endothelium. However, adhesion to extra-cellular matrix proteins, like FN, may also be important. FN binding is mediated by certain members of the VLA (beta 1 integrin) family of proteins. To investigate the role of Tc-FN interactions in synovitis the binding of synovial fluid (SF) and peripheral blood (PB) T cells to FN-coated wells, and the expression of cell surface VLA molecules on these cells by double label immunofluorescence, were studied. SF T cells bound better to FN than PB T cells. VLA alpha 4 and VLA beta 1 but not VLA alpha 5 were up-regulated on SF compared with PB T cells. Anti-VLA alpha 4, VLA beta 1 and VLA alpha 5 MoAbs inhibited the binding of SF T cells to FN. The increased binding of SF T cells to FN could have been related to activation and/or to their predominantly memory phenotype. Purified resting memory or naive T cells bound poorly to FN. In contrast, compared with SF T cells, concanavalin A-activated T cells showed a very similar level of binding to FN, comparable expression of VLA molecules and the same pattern of inhibition of binding to FN by MoAbs. Thus, VLA molecules may play an important role in the retention of T cells in the joint and since T cells can be activated via VLA-FN interactions, this mechanism may perpetuate chronic inflammation.
关节内T细胞的积聚是滑膜炎持续存在的原因。这一过程部分受与内皮细胞的选择性结合调节。然而，与细胞外基质蛋白（如纤连蛋白）的黏附也可能很重要。纤连蛋白结合由VLA（β1整合素）蛋白家族的某些成员介导。为了研究Tc-纤连蛋白相互作用在滑膜炎中的作用，研究了滑液（SF）和外周血（PB）T细胞与纤连蛋白包被孔的结合，以及通过双标记免疫荧光法检测这些细胞表面VLA分子的表达。SF T细胞比PB T细胞与纤连蛋白的结合更好。与PB T细胞相比，SF T细胞上的VLAα4和VLAβ1上调，而VLAα5未上调。抗VLAα4、VLAβ1和VLAα5单克隆抗体抑制SF T细胞与纤连蛋白的结合。SF T细胞与纤连蛋白结合增加可能与激活和/或其主要的记忆表型有关。纯化的静息记忆或初始T细胞与纤连蛋白的结合较差。相反，与SF T细胞相比，伴刀豆球蛋白A激活的T细胞与纤连蛋白的结合水平非常相似，VLA分子的表达相当，并且被单克隆抗体抑制与纤连蛋白结合的模式相同。因此，VLA分子可能在T细胞在关节中的滞留中起重要作用，并且由于T细胞可通过VLA-纤连蛋白相互作用被激活，这种机制可能使慢性炎症持续存在。
