Antigen-activated T cells inhibit cartilage proteoglycan synthesis independently of T-cell proliferation.
Previously we have shown that blood mononuclear cells (MNC) obtained from patients with rheumatoid arthritis (RA) have the capacity to induce depletion of proteoglycans (PG) in human cartilage explants. This was observed especially after stimulating MNC with mycobacterial antigens, rather than with the mitogen Concanavalin A (Con A). We have now co-cultured cartilage explants in the presence of T-cell clone A2b obtained from the rat model of adjuvant arthritis (AA). We show that inhibition of the cartilage PG synthesis is a consequence of antigen-specific T-cell activation and that it is mediated by a humoral factor. This seems to be a cytokine rather than an enzyme. Moreover, at the level of polyclonally responding T cells, inhibition of PG synthesis due to T-cell activation by mycobacterial antigens was shown to depend on prior mycobacterial immunization. Arthritogenic T-cell clone A2b also showed PG synthesis inhibitory effects when co-cultured with cartilage alone. The inhibitory activity was shown to be unrelated to the degree of T-cell proliferation. We conclude that antigen-specific T-cell activation may be one of the initiating events leading to cartilage damage in arthritic processes. The measurement of T-cell-mediated PG synthesis inhibition may be a more sensitive and relevant assay for the detection of pathogenic T cells than T-cell proliferation.
Wilbrink
B
B
Department of Rheumatology, University Hospital, Utrecht, The Netherlands.
Holewijn
M
M
Bijlsma
J W
JW
Van Roy
J L
JL
van der Zee
R
R
Boog
C J
CJ
Den Otter
W
W
Van Eden
W
W
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology; D002356:Cartilage / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D011509:Proteoglycans / Q000096:biosynthesis*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D006360:Heat-Shock Proteins; D011509:Proteoglycans