In vitro and in vivo reversal of thyroid epithelial polarity: its relevance for autoimmune thyroid disease.
A method is described for culturing intact human thyroid follicles, based on the study of 40 thyroidectomy specimens from normal (n = 18) and diseased glands (n = 22). Reversal of the normal polarity of thyrocytes, whereby the microvilli move from the colloid edge to the vascular pole of the cells, occurs gradually when the amount of fetal calf serum (FCS) is changed from 0.5% to 10%. The translocation of thyroid 'microvillar' antigens, (surface expression of 'microsomal' and a separate surface antigen) from the follicular to the vascular pole of thyrocytes was assessed by indirect immunofluorescence with human sera containing microsomal antibodies, as well as by electron microscopy. In normal and diseased thyroid glands up to 80% of follicles became reversed after 5-10 days in high FCS and the microsomal/microvillar antigen persisted for about twice as long as in monolayer cultures. Spontaneous reversal of polarity was observed in six of eight glands from patients with Graves' thyrotoxicosis or toxic nodular goitre in freshly dispersed tissues or after 2 days in 0.5% FCS, unlike normal tissues where only a trace of reversal appeared after 7 days of culture under these conditions. It is postulated that polarity reversal may play a role in human thyroid autoimmunity as the normally secluded 'microvillar' antigens becomes transposed to the vascular pole of thyroid follicles where they are in direct contact with cytotoxic antibodies or sensitized immunocytes. This could initiate lesions in intact follicles. Inappropriate HLA-DR expression on thyrocytes, either stimulated by phytohaemagglutinin (PHA) or appearing spontaneously as an early marker of thyroiditis, did not correlate with reversal of polarity.