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. 2001 May;44(5):1114-21.
doi: 10.1002/1529-0131(200105)44:5<1114::AID-ANR192>3.0.CO;2-B.

Fc epsilon receptor type I gamma chain replaces the deficient T cell receptor zeta chain in T cells of patients with systemic lupus erythematosus

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Fc epsilon receptor type I gamma chain replaces the deficient T cell receptor zeta chain in T cells of patients with systemic lupus erythematosus

E J Enyedy et al. Arthritis Rheum. 2001 May.

Abstract

Objective: T cells from the majority of patients with systemic lupus erythematosus (SLE) express significantly lower levels of T cell receptor zeta chain, a critical signaling molecule. However, TCR/CD3 triggering of SLE T cells shows increased phosphorylation of downstream signaling intermediates and increased [Ca2+]i response, suggesting the presence of alternative signaling mechanisms. We investigated whether Fcepsilon receptor type I gamma chain (FcepsilonRIgamma) could substitute for TCR zeta chain and contribute to T cell signaling in SLE.

Methods: T cells were purified from the peripheral blood of 21 patients with SLE and 5 healthy volunteers. The expression of FcepsilonRIgamma was investigated using immunoblotting, reverse transcriptase-polymerase chain reaction, and flow cytometry methods. Involvement of the FcepsilonRIgamma in T cell signaling was studied by immunoprecipitation and/or immunoblotting after TCR/CD3 stimulation.

Results: Western blotting and densitometric analysis showed that the expression of FcepsilonRIgamma in SLE T cells was 4.3-fold higher than in normal T cells (P < 0.001). Flow cytometric analyses of T lymphocyte subsets revealed that the proportions of FcepsilonRIgamma+,CD3+, FcepsilonRIgamma+,CD4+, and FcepsilonRIgamma+, CD8+ cells were significantly greater in SLE patients than in healthy controls (P < 0.001). Immunoprecipitation of SLE T cell lysates with an anti-FcepsilonRIgamma antibody showed that FcepsilonRIgamma associates with the tyrosine kinase Syk and the CD3epsilon chain, suggesting that FcepsilonRIgamma is functionally involved in TCR signaling.

Conclusion: These results demonstrate that the FcepsilonRIgamma chain is expressed at high levels in a large proportion of SLE T cells. The increased expression of FcepsilonRIgamma chain in SLE T cells may account in part for the aberrant antigen receptor-initiated signaling and contribute to the diverse cellular abnormalities found in this disease.

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