title: 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.
authors.affiliation: Department of Veterans Affairs Research Service, Columbia, MO 65212, USA. syu@astate.edu
authors.forename: Shiguang
authors.initials: S
authors.lastname: Yu
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Fang
authors.forename: Tumenjargal
authors.initials: T
authors.lastname: Sharav
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Sharp
authors.forename: Helen
authors.initials: H
authors.lastname: Braley-Mullen
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D006965:Hyperplasia; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009928:Organ Specificity / Q000276:immunology; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D013961:Thyroid Gland / Q000276:immunology* / Q000473:pathology*
chemical_list: D007371:Interferon-gamma