Antigen-specific B-cell function in human autoimmune thyroiditis.

T-B cells from the peripheral circulation of patients with autoimmune thyroiditis were cocultured with sheep red blood cells (SRBC) or soluble human thyroglobulin (Tg), a self-antigen. The B-cell mitogen, Staphylococcus aureus, combined with macrophage-derived B-cell differentiating factor, induced in vitro lymphoid activation and proliferation in the presence or absence of Tg or SRBC, which was monitored after 6 days by specific anti-Tg and anti-SRBC plaque-forming cell (PFC) responses (expressed as PFC per 10(6) T-B cells). In the presence of SRBC, significantly more anti-SRBC PFC (322 +/- 113, SE) were generated in normals (N = 5) compared with autoimmune thyroiditis patients (58 +/- 36) (N = 8) (P less than or equal to 0.001), data consistent with an antigen-specific T-cell defect. Anti-Tg PFC, not detectable in normal controls, were observed in patients in the absence (111 +/- 41) and presence (171 +/- 64) of Tg (10-1000 ng/ml). However, variable responses were noted after such coculture experiments with Tg. Three patients demonstrated amplification of anti-Tg PFC, while three showed antigen-related inhibition of anti-Tg PFC. These data indicated heterogeneity of responses to Tg antigen in patients with autoimmune thyroid disease compounded by significantly depressed antigen-specific induction mechanisms.