Diminished levels of T cell receptor ? chains in peripheral blood T lymphocytes from patients with systemic lupus erythematosus

Abstract

Objective To examine the expression of molecules known to participate in early T cell receptor (TCR)/CD3 signaling in peripheral blood (PB) T lymphocytes from patients with systemic lupus erythematosus (SLE). Methods Signaling molecules were analyzed by immunoprecipitation and Western blotting of unstimulated PB T lymphocyte cell lysates from SLE patients, non‐SLE disease controls, and healthy controls. Flow cytometry was used for analysis of the expression of membrane markers in intact cells. Results PB T lymphocytes from SLE patients showed diminished levels of TCRζ chains. This was not due to trapping of these molecules in the cytoskeleton, nor was it dependent on the presence of monocyte/macrophages. There was normal expression of CD3ε chains and normal assembly of TCR/CD3 complexes in membranes. We observed a lack of expression of TCRζ chains in in vitro cultures of SLE T cells, and reversal of the defective expression in some patients by culturing T cells in the presence of NH₄Cl. Conclusion Blood lymphocytes from SLE patients have a diminished expression of TCRζ chains that may be related to enhanced degradation in the lysosomal compartment. The defective expression of these molecules may alter signal transduction via the CD3 pathway and contribute to abnormal T cell responses in T lymphocytes from SLE patients.