Serum from patients with autoimmune diseases induces in vitro production of disease-associated antibodies by peripheral blood mononuclear cells from normal subjects.
Antibodies present in serum of patients with rheumatoid arthritis (RA), autoimmune thyroid diseases, and myasthenia gravis are preferentially cytotoxic to suppressor T lymphocytes from normal subjects induced by Concanavalin A. The aim of this study was to determine whether the lymphocytotoxic antibodies found in patients with these diseases also react with regulatory T cells to facilitate production of the autoantibodies responsible for each disease. Peripheral blood mononuclear cells (PBMC) from normal subjects were treated with serum from patients and complement. After washing, residual viable cells were cultured with pokeweed mitogen for 7 days. Immunoglobulin M rheumatoid factor and antihuman thyroglobulin antibody (anti-hTgAb) in the culture supernatants were measured by RIA. Anti-hTgAb was produced in culture supernatants of PBMC treated with serum samples from patients with autoimmune thyroid diseases, whereas serum samples from patients with RA, myasthemia gravis, or normal subjects did not stimulate production of detectable anti-hTgAb. In contrast, Immunoglobulin M rheumatoid factor was produced by normal PBMC treated only with serum from patients with RA. When normal T cells treated with serum were cultured with autologous untreated non-T cells in the presence of pokeweed mitogen, autoantibodies also were produced. Furthermore, the production of anti-hTgAb was suppressed by adding untreated T cells to the mixture of treated T cells and untreated non-T cells. These results suggest that lymphocytotoxic antibodies found in patients with autoimmune disorders may cause disease-associated suppressor T cell dysfunction.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D000961:Antilymphocyte Serum / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology; D013959:Thyroid Diseases / Q000276:immunology
D000961:Antilymphocyte Serum; D001323:Autoantibodies; D013954:Thyroglobulin