Immobilized anti-CD3 antibody activates T cell clones to induce the production of interstitial collagenase, but not tissue inhibitor of metalloproteinases, in monocytic THP-1 cells and dermal fibroblasts.
In this study we have investigated whether direct cell to cell contact between activated paraformaldehyde-fixed T cell clones obtained from synovial tissue of patients with osteoarthritis (OA) or rheumatoid arthritis and target monocytic cells or dermal fibroblasts influenced the balance between interstitial collagenase and its specific inhibitor tissue inhibitor of metalloproteinases (TIMP) produced by the latter cell types. PHA/PMA-activated fixed T cell clones or their membranes strongly induced the production of collagenase both in monocytic THP-1 cells and in dermal fibroblasts. In contrast, only low levels of TIMP were induced in THP-1 cells and no change of TIMP expression was observed in fibroblasts as a result of stimulation with PHA/PMA-activated T cells or T cell membranes. Anti-CD3-activated T cell clones stimulated the production of collagenase both in THP-1 cells and fibroblasts, whereas TIMP levels were not influenced. Collagenase production in THP-1 cells induced by anti-CD3-activated T cell clones was 1) dependent on the dose of anti-CD3 used to stimulate the T cells, 2) initiated only when CD3 was cross-linked, and 3) inhibited when cyclosporin A was included during T cell activation. Our data collectively indicate that activated T cells in contact with monocytic cells or fibroblasts may alter the balance between interstitial collagenase and its specific inhibitor TIMP. This selective induction of a mediator profile representative of matrix breakdown as a result of target cell interaction with activated T cells may be an important factor in the local process of tissue destruction that characterizes osteoarthritis and rheumatoid arthritis.
Miltenburg
A M
AM
Department of Medicine, University Hospital, Geneva, Switzerland.
Lacraz
S
S
Welgus
H G
HG
Dayer
J M
JM
D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002999:Clone Cells; D017364:Collagenases / Q000096:biosynthesis*; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005434:Flow Cytometry; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D020781:Matrix Metalloproteinase 1; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology; D010003:Osteoarthritis / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D006023:Glycoproteins; D010835:Phytohemagglutinins; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D020781:Matrix Metalloproteinase 1; D013755:Tetradecanoylphorbol Acetate