Helper and suppressor activities of lymphocyte subsets on antithyroglobulin production in vitro.

We studied the regulatory activities of T cells on specific antithyroglobulin (anti-Tg) and nonspecific immunoglobulin secretion in cultures of peripheral blood lymphocytes (PBL) of five patients with autoimmune thyroid diseases and high levels of serum anti-Tg. PBL were separated into a non-T population, including B-cells and monocytes, and a T-cell population by rosetting with sheep red cells. T-Cells were further separated into T helper (Th) and T suppressor (Ts) subsets by a panning technique using the monoclonal antibodies anti-Leu 3a and anti-Leu 2a, respectively. The three sets of cells, i.e. B, Th, and Ts, from patients and from normal individuals were cocultured in various combinations and stimulated with the polyclonal stimulant pokeweed mitogen. A sensitive plaque assay was used to enumerate cells producing anti-Tg and protein A-binding immunoglobulins. The PBL of both patients and normal individuals had Tg-specific suppressor cells. Ts-cells from patients in syngeneic or allogeneic combinations with B- and Th-cells at a ratio of 1:1:1 suppressed the pokeweed mitogen-induced anti-Tg response to 41 +/- 8% (+/-SE) and 50 +/- 20% of the control value, respectively, while Ts from normal individuals suppressed the response to 7 +/- 3% of the control value. The suppressive effect of the Ts-cells from patients and normal individuals on nonspecific immunoglobulin secretion was similar (reduced to 10-15% of control). Thus, there appeared to be a deficiency in Tg-specific suppressor activity in PBL of patients. On the other hand, Th-cells from patients (syngeneic or allogeneic) cocultured with patient B-cells produced a greater anti-Tg response than Th-cells from normal individuals. The helper activities of Th-cells of patients and normal individuals on nonspecific immunoglobulin secretion were similar. Thus, there appeared to be an increase in Tg-specific helper activity in PBL of patients.