IngentaConnect Defective expression and tyrosine phosphorylation of the T cell r...

Authors: PANG, M.; SETOYAMA, Y.¹; TSUZAKA, K.¹; YOSHIMOTO, K.¹; AMANO, K.¹; ABE, T.¹; TAKEUCHI, T.¹

Source: Clinical & Experimental Immunology, Volume 129, Number 1, July 2002 , pp. 160-168(9)

Abstract:

SUMMARY

We have reported that tyrosine phosphorylation and expression of the T cell receptor zeta chain (TCR ζ) was decreased in two systemic lupus erythematosus (SLE) patients with an abnormal TCR ζ lacking exon-7. To examine further the TCR ζ defect and any possible relationship with specific clinical features, we studied the expression of TCR ζ 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 ζ in SLE (P < 0·001), but not in the other rheumatic diseases. Immunoprecipitation experiments confirmed that the expression of TCR ζ in SLE T cells was decreased dramatically (normal: 111·4 ± 22·6%, SLE: 51·6 ± 37·4%, P < 0·0001). The decrease in TCR ζ 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 ζ expression normalized after treatment, suggesting that mechanisms responsible for the TCR ζ defect appear to be heterogeneous. These results confirm the defective expression and altered tyrosine phosphorylation of TCR ζ in a large proportion of SLE patients, suggesting that it may play an important role in T cell dysfunction in SLE.

Keywords: autoimmunity signal transduction TCR-zeta chain tyrosine phosphorylation

Document Type: Research article

DOI: 10.1046/j.1365-2249.2002.01833.x

Affiliations: 1: Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Kawagoe, Saitama, Japan, and

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Defective expression and tyrosine phosphorylation of the T cell receptor zeta chain in peripheral blood T cells from systemic lupus erythematosus patients