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

Objective. To examine the expression of molecules known to participate in e arly T cell receptor (TCR)/CD3 signaling in peripheral blood (PB) T lymphoc ytes from patients with systemic lupus erythematosus (SLE). Methods. Signaling molecules were analyzed by immunoprecipitation and Weste rn blotting of unstimulated PB T lymphocyte cell lysates from SLE patients, non-SLE disease controls, and healthy controls. Flow cytometry was used fo r analysis of the expression of membrane markers in intact cells. Results. PB T lymphocytes from SLE patients showed diminished levels of TCR zeta chains. This was not due to trapping of these molecules in the cytosk eleton, nor was it dependent on the presence of monocyte/macrophages. There was normal expression of CD3 epsilon chains and normal assembly of TCR/CD3 complexes in membranes. We observed a lack of expression of TCR zeta chain s in in vitro cultures of SLE T cells, and reversal of the defective expres sion in some patients by culturing T cells in the presence of NH4Cl. Conclusion. Blood lymphocytes from SLE patients have a diminished expressio n of TCR zeta chains that may be related to enhanced degradation in the lys osomal compartment. The defective expression of these molecules may alter s ignal transduction via the CD3 pathway and contribute to abnormal T cell re sponses in T lymphocytes from SLE patients.