Studies on the Immunoregulation of Anti-Thyroglobulin Antibody Synthesis by Lymphocytes in the Patients with Hashimoto's Disease and Graves' Disease

Abstract

Anti-thyroglobulin antibody (aTg) synthesis by the lymphocytes in the peripheral blood and the thyroid gland were studied in patients with Hashimoto's disease (HD) or Graves' disease (GD), all in euthyroid states, to clarify the mechanism of autoantibody synthesis. The ability of the lymphocytes to synthesize aTg was analyzed in the culture system of lymphocytes incubated in a concentration of 1 X 10(6) cells/ml for 7 days at 37 degrees C in 5% CO2-95% air. The B cells alone were also cultured in the absence of T cells or PWM to estimate their abilities on spontaneous aTg synthesis. The regulatory functions of T cells on aTg synthesis by B cells were investigated in cross-combination cultures of B cells and an equal number of T cells. The concentration of aTg and total IgG in cultured medium were measured by sensitive enzyme immunoassay developed by us, and the capacity on aTg synthesis was expressed as aTg/IgG ratio (aTg%). The surface markers of lymphocytes in the peripheral blood and the thyroid gland were determined by flowcytometry using mouse monoclonal antibodies (CD3, CD4, CD8, OKIa1, CD20 and Leu7). These results were obtained as follows: 1) All the lymphocytes from the peripheral blood, thyroid gland and bone marrow of HD patients synthesized much more aTg (3.1 +/- 1.6, 2.2 +/- 0.9, 1.5 +/- 0.5%, respectively) than those from normal peripheral blood lymphocytes (1.0 +/- 0.9%). This hyper-function of aTg synthesis by the lymphocytes in HD patients was caused by the presence of activated B cells and the predominance of helper T cells. 2) Both the lymphocytes from the peripheral blood and the thyroid gland in GD patients synthesized the same level of aTg (0.7 +/- 0.7%) as in normal subjects. However, the lymphocytes from bone marrow and lymph nodes, which were indicated by Benner et al. to play a main role in antibody synthesis after immunization with antigen, were involved in aTg synthesis (1.8 +/- 1.2, 5.4 +/- 1.1%, respectively). 3) There was no correlation between aTg synthesis and CD4+/CD8+ ratio of the peripheral blood lymphocytes in AITD patients. These results suggest that aTg synthesis in HD patients is an expression of abnormal immune reaction due to the presence of aTg specific activated B cells and dysfunction of regulatory T cells, and that aTg production by the lymphocytes from the bone marrow and lymph nodes in GD patients is resulted from a normal immune response to the high level of thyroglobulin in the blood.(ABSTRACT TRUNCATED AT 400 WORDS)