Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by transfer of thyroglobulin-primed in vitro activated splenocytes. Thyroid lesions reach maximal severity 20 days later, and inflammation resolves or progresses to fibrosis by day 60 depending on the extent of thyroid damage at day 20. Depletion of CD8+ T cells inhibits G-EAT resolution. We showed that expression of FLICE (Fas-associated death domain-like IL-1-converting enzyme) inhibitory protein (FLIP) transgene (Tg) on thyroid epithelial cells (TEC) of DBA/1 mice had no effect on G-EAT induction, but promoted earlier resolution of G-EAT. However, when CBA/J WT donor cells were transferred to transgenic CBA/J mice expressing FLIP on TEC, they developed less severe G-EAT than FLIP Tg- littermates. Both strains expressed similar levels of the FLIP transgene, but endogenous FLIP was upregulated to a greater extent on infiltrating T cells during G-EAT development in DBA/1 compared to CBA/J mice. Following transient depletion of CD8+ T cells, FLIP Tg+ and Tg- CBA/J recipients both developed severe G-EAT at day 20. Thyroid lesions in CD8-depleted Tg+ recipients were resolving by day 60, whereas lesions in Tg- littermates did not resolve and most were fibrotic. FLIP Tg+ recipients had increased apoptosis of CD3+ T cells compared to Tg- recipients. The results indicate that transgenic FLIP expressed on TEC in CBA/J mice promotes G-EAT resolution, but induction of G-EAT is inhibited unless CD8+ T cells are transiently depleted.