T cells bound by vascular cell adhesion molecule-1/CD106 in synovial fluid in rheumatoid arthritis: inhibitory role of soluble vascular cell adhesion molecule-1 in T cell activation.
Elevated levels of soluble vascular cell adhesion molecule-1 (sVCAM-1)/CD106 have been reported in synovial fluid (SF) from patients with rheumatoid arthritis (RA). In the present study, VCAM-1-positive lymphocytes were found in SF from RA patients. The data strongly suggest that sVCAM-1 might be bound to lymphocytes in SF. rsVCAM-1 in the fluid phase can bind to both SF lymphocytes and IL-2-dependent T cell lines with up-regulated expression and binding activity of VLA-4. Furthermore, proliferative responses of SF mononuclear cells (SFMC) with PHA, immobilized anti-CD3, or anti-CD2 and PMA were inhibited to various extents in the presence of rsVCAM-1, but only PMA-induced proliferative response of PBMC from normal individuals was inhibited notably in the presence of rsVCAM-1. rsVCAM-1 also drastically reduced IL-2 production of Jurkat leukemic T cells possessing high affinity VLA-4 with the stimulation of anti-CD3 and PMA, suggesting that the T cell hyporesponsiveness induced by rsVCAM-1 might stem from impairment of IL-2 production. These results indicate that sVCAM-1 provides a negative signal to T cell activation, probably by affecting the pathway of protein kinase C activation. Thus, binding of sVCAM-1 to SF lymphocytes might partly explain the anergic state of these lymphocytes.
Kitani
A
A
Department of Immunology and Medical Zoology, School of Medicine, Kagoshima University, Japan.
Nakashima
N
N
Matsuda
T
T
Xu
B
B
Yu
S
S
Nakamura
T
T
Matsuyama
T
T
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012995:Solubility; D013582:Synovial Fluid / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1