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

Objective. T cells from the majority of patients with systemic lupus erythe matosus (SLE) express significantly lower levels of T cell receptor zeta ch ain, a critical signaling molecule. However, TCR/CD3 triggering of SLE T ce lls shows increased phosphorylation of downstream signaling intermediates a nd increased [Ca2+](i) response, suggesting the presence of alternative sig naling mechanisms. We investigated whether Fee receptor type I gamma chain (Fc epsilon RI gamma) 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 wit h SLE and 5 healthy volunteers. The expression of Fc epsilon RI gamma was i nvestigated using immunoblotting, reverse transcriptase-polymerase chain re action, and flow cytometry methods. Involvement of the Fc epsilon RI gamma in T cell signaling was studied by immunoprecipitation and/or immunoblottin g after TCR/CD3 stimulation. Results. Western blotting and densitometric analysis showed that the expres sion of Fc epsilon RI gamma in SLE T cells was 4.3-fold higher than in norm al T cells (P < 0.001). Flow cytometric analyses of T lymphocyte subsets re vealed that the proportions of Fc<epsilon>RI gamma+,CD3+, Fc epsilon RI gam ma+,CD4+, and Fc epsilon RI gamma+, CD8+ cells were significantly greater i n SLE patients than in healthy controls (P < 0.001). Immunoprecipitation of SLE T cell lysates with an anti-Fc<epsilon>RI gamma antibody showed that F c epsilon RI gamma associates with the tyrosine kinase Syk and the CD3 epsi lon chain, suggesting that Fc epsilon RI gamma is functionally involved in TCR signaling. Conclusion. These results demonstrate that the Fc epsilon RI gamma chain is expressed at high levels in a large proportion of SLE T cells. The increas ed expression of Fc epsilon RI gamma chain in SLE T cells may account in pa rt for the aberrant antigen receptor-initiated signaling and contribute to the diverse cellular abnormalities found in this disease.