Regulated expression of activated leukocyte cell adhesion molecule, a ligand for cd6, in rheumatoid arthritis synovium
CD6, a 130 kDa glycoprotein expressed on the surface of T cells and a subset of B cells, is involved in TCR-mediated T cell activation and has been implicated in mediating autoreactive immune responses. We have recently identified a 100 kDa glycoprotein ligand for CD6 that has been named Activated Leukocyte Cell Adhesion Molecule (ALCAM) because this CD6 ligand is upregulated on activated leukocytes in vitro. We used indirect immunofluorescence, 3-coIor flow cytometry, and synoviocyte-T cell binding assays to determine if ALCAM was functionally expressed in the synovium of patients with rheumatoid arthritis (RA). While ALCAM was undetectable in non-inflammatory synovium from patients with trauma (N=3), ALCAM was detectable at low levels on type A synovial lining cells from 2/4 patients with severe osteoarthritis (OA), and at higher levels on type A synovial lining cells from all patients with RA (N=9). ALCAM was not detected on most CD14+ tissue macrophages, but was expressed at high levels on multinucleated giant cells in RA synovial tissues with chronic granulomatous inflammation (N=2), on CD14+ synovial fluid monocytes (N=3) and on cultured synovial fibroblasts (N=4). ALCAM was not present on CD3+ lymphocytes within synovium (N=16) or synovial fluid (N=3). Antibodies to CD6 and ALCAM did not significantly inhibit RA synoviocyte-PBMC binding, but did inhibit RA synovial fibroblast-thymocyte binding by 38 ±12% and 51 ±11%, respectively (p < 0.05). These data suggest that the regulated expression of the novel CD6 ligand ALCAM in RA may function to selectively transduce signals through T cell CD6 in infiammed versus non-inflammed synovium, and may contribute to the pathogenesis of RA.
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- General Clinical Medicine
- 3202 Clinical sciences
- 1103 Clinical Sciences
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Published In
ISSN
Publication Date
Volume
Issue
Related Subject Headings
- General Clinical Medicine
- 3202 Clinical sciences
- 1103 Clinical Sciences