DECREASED EXPRESSION OF SIGNAL-TRANSDUCING CD3-ZETA CHAINS IN T-CELLSFROM THE JOINTS AND PERIPHERAL-BLOOD OF RHEUMATOID-ARTHRITIS PATIENTS

Although T cells from patients with rheumatoid arthritis (RA) have pre viously been determined to have poor proliferative responses to a vari ety of stimuli, the underlying mechanism is not known. We have investi gated the expression of the signal-transducing zeta molecule in subset s of T cells and natural killer (NK) cells derived from the peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells ( SFMC) of RA patients using quantitative flow cytometry, Western blot a nalysis and immunohistochemistry. A decrease of zeta expression was ap parent in all investigated lymphocyte subsets from the PBMC and SFMC o f RA patients, as compared to the corresponding subsets from healthy a ge-and sex-matched controls. A less pronounced reduction of cell surfa ce-located CD3 epsilon, CD4 and CD8 was also located in T cells from S FMC as compared to PBMC from RA patients. Biochemical demonstration of the low or absent CD3 zeta in PBMC from patients with RA was achieved by Western blot analysis. Immunohistochemical staining and image anal ysis also confirmed the low expression of zeta chains in synovial tiss ue of RA patients. The possibility that the decreased expression of ze ta and of immune functions of T cells from RA patients may be related to the presence of free oxygen radiclals, as we have previously report ed in cancer patients, should be considered.