Studies of human peripheral blood mononuclear cells (PBMC) from patients with subacute thyroiditis in severe combined immunodeficient (SCID) mice: less production of human interferon gamma than that seen for Graves' disease.

Abstract

Human peripheral blood mononuclear cells (PBMC) from 2 patients with de Quervain's subacute thyroiditis (SAT), 2 with Graves' disease (GD), and 3 normal persons (N) were engrafted into severe combined immunodeficient (SCID) mice so as to study whether SAT PBMC would differ immunologically from GD PBMC in vivo. Human IgG was detected in all mice engrafted with PBMC from either group of patients or normal persons. Thyroid Stimulating Antibody (TSAb) was detected in the sera of mice with PBMC from SAT or GD patients, but not N. Thyroperoxidase (TPO)-antibody (Ab) and/or thyroglobulin (Tg)-Ab was detectable in the mice with GD PBMC only, but not in those with SAT or normal PBMC. The production of interferon gamma (IFN gamma) in mice engrafted with N PBMC was 8, 13 and 14 U/ml, similar to values found in sera of SCID mice with SAT PBMC (14 and 11 U/ml), i.e., much lower than that seen for GD PBMC (127 and 78 U/ml); this is consistent with the view that, compared to GD T lymphocytes, that there is probably a lower number of T lymphocytes sensitized to the thyrotrophin (TSH) receptor antigen in SAT patients. Another possibility is that the transient thyroidal antigenic release seen in the acute (hyperthyroid) phase may be insufficient for adequate T cell sensitization. Still other possibilities include the effect of more severe hyperthyroidism of GD on T cell sensitization, and CD4/CD8 cell ratios. In any event, these results are consistent with our previous view that antigenic release in SAT will not itself lead to autoimmune thyroid disease.