Apoptosis of thyrocytes and effector cells during induction and resolutionof granulomatous experimental autoimmune thyroiditis

Experimental autoimmune thyroiditis (EAT) with granulomatous histopathology (G-EAT) can be induced by cells from mouse thyroglobulin (MTg)-immunized d onors activated in vitro with MTg and IL-12, G-EAT lesions reach maximum se verity 18-21 days after cell transfer and, if some thyroid follicles remain , lesions almost completely resolve by day 35. CD8(+) cells are required fo r G-EAT resolution. To begin to determine the mechanisms involved in G-EAT resolution, apoptosis in thyroids was analyzed by TUNEL staining. Apoptotic thyrocytes and inflammatory cells were present in the thyroids of both CD8 (+) and CD8-depleted recipient mice at day 19-21. By day 35, apoptotic cell s were rare in thyroids of mice whose lesions had resolved; the few apoptot ic inflammatory cells were generally in close proximity to thyroid follicle s. Thyroids of CD8-depleted mice had ongoing inflammation at day 35 and mos t apoptotic cells were thyroid follicular cells. The expression of Fas and Fas ligand (FasL) mRNA in thyroids was also determined by RT-PCR in both CD 8(+) and CD8-depleted recipient mice. Fas was expressed in normal thyroids and its expression was relatively constant throughout the course of disease . FasL mRNA was not expressed in normal thyroids. FasL mRNA expression gene rally correlated with G-EAT severity, being maximal at day 21 and diminishi ng as lesions resolved. However, FasL mRNA expression in thyroids of CD8-de pleted mice in which resolution was delayed was decreased compared to thyro ids of CD8(+) mice with comparable disease severity, suggesting that FasL e xpressed by CD8(+) cells may play a role in G-EAT resolution.