CD8+ T Cells Induce Thyroid Epithelial Cell Hyperplasia and Fibrosis

Abstract

CD8+ T cells can be important effector cells in autoimmune inflammation, generally because they can damage target cells by cytotoxicity. This study shows that activated CD8+ T cells induce thyroid epithelial cell hyperplasia and proliferation and fibrosis in IFN-γ−/− NOD.H-2h4 SCID mice in the absence of CD4+ T cells. Because CD8+ T cells induce proliferation rather than cytotoxicity of target cells, these results describe a novel function for CD8+ T cells in autoimmune disease. In contrast to the ability of purified CD8+ T cells to induce thyrocyte proliferation, CD4+ T cells or CD8 T cell-depleted splenocytes induced only mild thyroid lesions in SCID recipients. T cells in both spleens and thyroids highly produce TNF-α. TNF-α promotes proliferation of thyrocytes in vitro, and anti–TNF-α inhibits development of thyroid epithelial cell hyperplasia and proliferation in SCID recipients of IFN-γ−/− splenocytes. This suggests that targeting CD8+ T cells and/or TNF-α may be effective for treating epithelial cell hyperplasia and fibrosis.