Thyroid regeneration and EAT progression in CBA/J mice. Thyroid infiltration (left y-axis, ▪) and regeneration (right y-axis, ○) are shown as mean ± se according to the day after thyroglobulin immunization.

Scores of EAT and thyroidal function in CD24-H2^k knockout mice and wild-type controls. A, Infiltration scores. EAT develops similarly in CD24-H2^k knockout mice (○) and wild-type controls (•) but ameliorates more rapidly in the absence of CD24. B, Capsular involvement scores. CD24-H2^k knockout mice (○) feature a more severe infiltration of the perithyroidal capsule than wild-type littermates (•) during the initiation of EAT. C, Thyroid regeneration scores in CD24-H2^k knockout (○) and wild-type littermates (•). D, Serum T₄ levels in CD24-H2^k knockout (○) and wild-type littermates (•).

Serum T₄ and thyroglobulin antibodies during EAT of CBA/J mice. A, Thyroid function changes repeatedly after immunization; it decreases initially due to the nonthyroidal illness (NT) effect, remains low during the destructive phase of EAT, then increases transiently, and finally normalizes after d 70. B, IgG2a thyroglobulin-specific antibodies. Thyroglobulin antibodies increase as expected after immunization and remain elevated up to 3 months thereafter. C, T₄ levels positively and significantly correlates with thyroglobulin antibody levels.

PCNA expression, BrdU uptake, and Oct-4 expression during EAT of CBA/J mice. A, High level of PCNA expression is observed in thyroid on d 35 after immunization. Dark brown nuclei represent PCNA positivity. PCNA-positive cells with high grade locate in follicles arose as rosettes rather than a connective tissue framework. The inset shows for comparison PCNA-negative thyrocytes before immunization. B, PCNA-positive cells decrease in thyroid on d 100 after immunization. Most of thyrocytes (follicular cells) are PCNA negative. C, Regenerating thyrocytes are BrdU positive on d 35 after immunization. Dark blue nuclei represent BrdU positivity. The inset shows for comparison BrdU-negative thyrocytes before immunization. D, Oct-4 mRNA expression by semiquantitative PCR. Note the decrease in Oct-4 transcript on d 35 after immunization.

CD24 expression on the thyroid and EAT development in CD24-H2^k knockout mice and wild-type controls. A, CD24 is expressed in normal baseline thyroids and throughout the course of EAT. B, CD24 clearly identifies the regenerating thyrocytes on d 35 after immunization. C, Gross appearance of the thyroid gland in the two genotypes during the initiation of EAT. Note the more severe infiltration of the perithyroidal soft tissues in the CD24-deficient genotype. D, Day 14 after immunization in CD24-H2^k knockout mice, hematoxylin and eosin (H&E) stain; magnification, ×20. Note the severe infiltration of the thyroid and the perithyroidal structures. E, Day 42 after immunization in wild-type littermates, H&E stain; magnification, ×20. The thyroid has recovered its normal architecture but still shows foci of infiltration, whereas it was completely normal in CD24-H2^k knockout mice (not shown).

A, Day 10 after immunization, hematoxylin and eosin (H&E) stain; magnification, ×20. Infiltration of mononuclear cells started around vessel (arrow). B, Day 14 after immunization, H&E stain; magnification, ×20. Note the massive infiltration of the thyroid with hematopoietic cells, extending also to the perithyroidal tissues (arrows), and the loss of thyroid follicles. The inset shows the presence of colloidal micro-abscesses. C, Day 35 after immunization, H&E stain; magnification, ×40. Note the appearance of compact, cellular, regenerating thyroid follicles. The higher magnification shows that at this stage, the infiltrate is mainly mononuclear in nature. The inset shows intrafollicular macrophages that stain positive for F4/80. D, Day 70 after immunization, H&E stain; magnification, ×20. The thyroid has largely restored its follicular architecture, and many small follicles are observed. E, Day 100 after immunization, H&E stain; magnification, ×20. The thyroid has largely restored its follicular architecture, although foci of mononuclear infiltration remain. F, Day 35 after immunization, van Gieson stain; magnification, ×20. The stain highlights the largely conserved connective tissue framework among which appear the budding thyroid follicles.