Altered expression of the T cell receptor-CD3 complex in systemic lupus erythematosus.
SLE T cells may play a key role in autoantibody production in SLE B cells. In addition, accumulating evidence has shown that SLE T cells participate in the attack on target cells or tissues through the overproduction of pro-inflammatory cytokines or an increase in cell-to-cell adhesion. Thus, the functional abnormality of SLE T cells appears to be pivotal to an understanding of SLE pathogenesis. Accumulating evidence suggests that potential defects may reside in the proximal signal transduction around the TCR-CD3 complex. We have demonstrated that the expression of TCR zeta chain is significantly decreased in peripheral blood T cells from SLE patients. To explore the mechanism of defective expression of TCR zeta chain, we examined mRNA of TCR zeta, and found that two alternatively spliced variants such as exon 7 (-) and short 3'-UTR are detected in SLE. We review the possible role of the TCR zeta defects in autoimmunity and discuss how the splicing variants lead to downregulated protein expression of TCR zeta chain.
Takeuchi
Tsutomu
T
Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Kawagoe, Saitama, Japan. tsutake@saitama-med.ac.jp
Tsuzaka
Kensei
K
Abe
Tohru
T
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D015551:Autoimmunity; D003095:Collagen Diseases / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D008565:Membrane Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain