T lymphocyte adhesion to fibronectin (FN): a possible mechanism for T cell accumulation in the rheumatoid joint.
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.
Rodriguez
R M
RM
Division of Medicine, United Medical School, London, UK.
Pitzalis
C
C
Kingsley
G H
GH
Henderson
E
E
Humphries
M J
MJ
Panayi
G S
GS
D001172:Arthritis, Rheumatoid / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D016023:Integrins / Q000502:physiology; D008213:Lymphocyte Activation; D010641:Phenotype; D016029:Receptors, Very Late Antigen / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000648:ultrastructure; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
D005353:Fibronectins; D016023:Integrins; D016029:Receptors, Very Late Antigen