Defective expression and tyrosine phosphorylation of the T cell receptor zeta chain in peripheral blood T cells from systemic lupus erythematosus patients.
We have reported that tyrosine phosphorylation and expression of the T cell receptor zeta chain (TCR zeta) was decreased in two systemic lupus erythematosus (SLE) patients with an abnormal TCR zeta lacking exon-7. To examine further the TCR zeta defect and any possible relationship with specific clinical features, we studied the expression of TCR zeta in peripheral blood T cells from 44 patients with SLE, 53 with other rheumatic diseases (30 rheumatoid arthritis (RA), 11 systemic sclerosis (SSc) and 12 primary Sjögren's syndrome(SjS)) and 39 healthy individuals. Flow cytometric analysis demonstrated a significant decrease in the expression of TCR zeta in SLE (P < 0.001), but not in the other rheumatic diseases. Immunoprecipitation experiments confirmed that the expression of TCR zeta in SLE T cells was decreased dramatically (normal: 111.4 +/- 22.6%, SLE: 51.6 +/- 37.4%, P < 0.0001). The decrease in TCR zeta did not correlate with disease activity, or with the dose of prednisolone (PSL). There were, however, three SLE patients in whom the level of TCR zeta expression normalized after treatment, suggesting that mechanisms responsible for the TCR zeta defect appear to be heterogeneous. These results confirm the defective expression and altered tyrosine phosphorylation of TCR zeta in a large proportion of SLE patients, suggesting that it may play an important role in T cell dysfunction in SLE.
Pang
M
M
Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Kawagoe, Japan.
Setoyama
Y
Y
Tsuzaka
K
K
Yoshimoto
K
K
Amano
K
K
Abe
T
T
Takeuchi
T
T
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015551:Autoimmunity; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010766:Phosphorylation; D011239:Prednisolone / Q000627:therapeutic use; D011499:Protein Processing, Post-Translational; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D007166:Immunosuppressive Agents; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D011239:Prednisolone