Thyrocyte class I and class II upregulation is a secondary phenomenon and does not contribute to the pathogenesis of autoimmune thyroid disease.

It has been proposed elsewhere that thyrocyte (TEC) class I expression plays a central role in the pathogenesis of autoimmune thyroid disease (AITD). We have studied thyroid xenografts from patients with Graves' disease (GD) and normal (paranodular) (N) tissues in nude and severe combined immunodeficient (SCID) mice. TEC class I and II expression are markedly increased in GD, as compared with N thyroids. When these tissues are transplanted to nude mice in which the immune environment is deleted from the thyroid grafts, TEC class I and class II expression decline to low levels; interferon-gamma (IFN-gamma) but not interferon-alpha (IFN-alpha) will then upregulate TEC class I and class II expression in these N and GD nude xenografts. In SCID mouse xenografts, GD tissue shows higher TEC class I and II expression compared with N. In these SCID mice, both IFN-alpha and IFN-gamma will stimulate TEC class I and II expression further in both GD and N. However, only IFN-alpha increases thyroid antibody (TAb) production from GD SCID grafts, whereas IFN-gamma causes a rise in GD TEC class I and II expression, but no significant increase in TAb. Moreover, in N SCID grafts, despite a rise in TEC class I and II expression induced by both IFNs, no TAb could be detected. Because an immune environment is necessary for TEC class I and II upregulated expression, we conclude that such upregulation is a secondary phenomenon. Because there was dissociation between the stimulation of TEC class I and II expression versus the production of TAb, then at least under these experimental conditions, there is no support for a role for TEC class I and class II upregulation in the pathogenesis of AITD.