Fcϵ receptor type I γ chain replaces the deficient T cell receptor ζ chain in T cells of patients with systemic lupus erythematosus

Objective T cells from the majority of patients with systemic lupus erythematosus (SLE) express significantly lower levels of T cell receptor ζ chain, a critical signaling molecule. However, TCR/CD3 triggering of SLE T cells shows increased phosphorylation of downstream signaling intermediates and increased [Ca 2+ ] i response, suggesting the presence of alternative signaling mechanisms. We investigated whether Fcϵ receptor type I γ chain (FcϵRIγ) could substitute for TCR ζ 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 FcϵRIγ was investigated using immunoblotting, reverse transcriptase–polymerase chain reaction, and flow cytometry methods. Involvement of the FcϵRIγ 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 FcϵRIγ 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 FcϵRIγ+,CD3+, FcϵRIγ+,CD4+, and FcϵRIγ+, CD8+ cells were significantly greater in SLE patients than in healthy controls ( P < 0.001). Immunoprecipitation of SLE T cell lysates with an anti‐FcϵRIγ antibody showed that FcϵRIγ associates with the tyrosine kinase Syk and the CD3ϵ chain, suggesting that FcϵRIγ is functionally involved in TCR signaling. Conclusion These results demonstrate that the FcϵRI γ chain is expressed at high levels in a large proportion of SLE T cells. The increased expression of FcϵRI γ 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.