[Thyroglobulin (Tg)-specific induction of IL2 responsiveness in lymphocytes from patients with Hashimoto thyroiditis and its dependency on HLA-DQ antigen].

The peripheral blood mononuclear cells from Hashimoto thyroiditis patients acquired IL2 responsiveness in response to thyroglobulin stimulation, when they were partially depleted of adherent cells. Non-adherent cells reconstituted with Tg-pulsed autologous adherent cells at the ratio of 9:1 also acquired IL2 responsiveness, but those cultured with OVA (ovalbumin)-pulse adherent cells did not. This indicates Tg-induced IL2 responsiveness was specific for the antigen. Although there was no clear correlation between the intensity of induced IL2 responsiveness and the serum titer of anti-Tg antibody, Tg-induced IL2 responsiveness was significant in the seropositive patients. Pretreatment of the mononuclear cells with the monoclonal antibody to the HLA-DQ framework (Leu 10), but not the HLA-DR framework (OKIal), blocked the induction of IL2 responsiveness. This indicated that DQ-bearing adherent cells play a key role in presenting Tg antigen to the responder cells.

Heterogeneity of the immune status concerning anti-thyroglobulin antibody production among patients with Hashimoto's thyroiditis; an in vitro study.

In vitro anti-thyroglobulin antibody (TgAb) production by unstimulated, thyroglobulin (Tg)-stimulated and pokeweed mitogen (PWM)-stimulated peripheral blood lymphocytes (PBL) from 44 patients with Hashimoto's thyroiditis and 10 normal individuals was investigated using a biotin-avidin enzyme-linked immunosorbent assay. Spontaneous TgAb production by non-T cells alone was observed in some patients. TgAb production induced by Tg was T cell-dependent and not accompanied by nonspecific IgG production. PBL from normal individuals produced no TgAb under any conditions. The patients were divided into four groups: 24 showed no TgAb production under any conditions, eight showed TgAb production only with PWM, seven produced TgAb spontaneously and more with both Tg and PWM, and five showed spontaneous TgAb production but no increase with Tg (four of these five patients showed an increase with PWM). Significant positive correlations between the serum TgAb titre and the amounts of TgAb produced by unstimulated, and Tg-stimulated and PWM-stimulated PBL were observed. It was suggested that spontaneous TgAb production was due to in vivo triggered antibody-producing B cells, while the TgAb produced only after in vitro Tg stimulation would be due to Tg-specific memory B cells helped by Tg-specific T cells. The increase in TgAb production due to PWM may be caused by activation of nonspecific helper T cells. These different PBL profiles probably reflect the heterogeneity of the immune status concerning TgAb production among patients with Hashimoto's thyroiditis.

In vitro detection of anti-thyroglobulin antibody forming cells from the lymphocytes of chronic thyroiditis patients and analysis of their regulation.

Anti-thyroglobulin (anti-Tg) antibody forming cells were detected by plaque forming cell (PFC) assay, using B cells depleted of sheep erythrocyte (SRBC) binding cells and T cells separated without SRBC interaction. When 2 x 10(5) non-T cells were combined with the same number of T cells from chronic thyroiditis patients, more than 20 PFC were detected; few, if any, PFC developed from normal lymphocytes. T cells were generally needed to produce quantifiable PFC, suggesting that helper T cells are required for this autoantibody formation. A positive relationship existed between the number of PFC and the serum anti-Tg antibody titres of the same patients. The generation of Tg-specific PFC from patient lymphocytes was markedly suppressed by normal T cells or T cells from patients whose lymphocytes did not produce PFC. The same level of suppression was also seen on the addition of culture supernatant from Tg antigen stimulated T cells. Autologous T cells, from patients whose lymphocytes produced PFC, did not show such suppressor effects, suggesting that in chronic thyroiditis patients, the regulatory T cell function preventing anti-Tg autoantibody formation is impaired.