Suppressor-cell dysfunction in systemic lupus erythematosus. Cells involved and in vitro correction.
To characterize the cell(s) responsible for the suppressor-cell dysfunction in active systemic lupus erythematosus (SLE), we fractionated blood mononuclear cells into thymus-derived (T), bone marrow-derived (B), and monocyte-depleted populations. Various cell populations from active SLE, inactive SLE, or normals, were activated with Concanavalin A, washed, and then co-cultured with active SLE cells. Soluble immune response suppressor (SIRS) from culture supernates of the activated cells was also used for the possible correction of the suppressor-cell dysfunction. Suppression was tested by enumerating DNA-binding cells by radioautography and by quantitating anti-DNA antibody in culture supernates by radioimmunoassay; and immunoglobulin was tested in cells and supernates by the immunofluorescence and the immunofluor techniques, respectively. Except for the numbers of DNA-binding cells, which were not suppressed, all the other three parameters in co-cultures with cells from active SLE patients were suppressed by Concanavalin A-activated cells (P < 0.001), or by SIRS (P < 0.05) from normals or inactive SLE patients. Concanavalin A-activated autologous or allogeneic active SLE cells and nonactivated cells from active or inactive SLE failed to suppress the various B-cell functions. Nonactivated normal cells suppressed levels of anti-DNA and immunoglobulin in supernates (P < 0.05). In characterizing the cells responsible for the suppressor dysfunction, it was clear from the results that T cells responsive to Concanavalin A activation are deficient in active SLE and fail to generate SIRS. On the other hand, monocytes from active SLE patients are responsive to signals from the activated T cells of normals or inactive SLE donors. Because SIRS suppresses active SLE cells in vitro, it might be considered therapeutically for the in vivo modulation of SLE.
D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007165:Immunosuppression Therapy; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D003208:Concanavalin A