title: Culture promotes transfer of thyroid epithelial cell hyperplasia and proliferation by reducing regulatory T cell numbers.
abstract: IFN-γ(-/-) NOD.H-2h4 mice develop a spontaneous autoimmune thyroid disease, thyroid epithelial cell hyperplasia and proliferation (TEC H/P) when given NaI in their water for 7+ mo. TEC H/P can be transferred to IFN-γ(-/-) SCID mice by splenocytes from mice with severe (4-5+) disease, and transfer of TEC H/P is improved when splenocytes are cultured prior to transfer. Older (9+ mo) IFN-γ(-/-) NOD.H-2h4 mice have elevated numbers of FoxP3(+) T reg cells, up to 2-fold greater than younger (2 mo) mice. During culture, the number of T reg decreases and this allows the improved transfer of TEC H/P. Co-culture with IL-2 prior to transfer prevents the decrease of T reg and improves their in vitro suppressive ability resulting in reduced TEC H/P in recipient mice. Therefore, culturing splenocytes improves transfer of TEC H/P by reducing the number of T reg and IL-2 inhibits transfer by preserving T reg number and function.
authors.affiliation: Department of Internal Medicine, University of Missouri, One Hospital Drive, Med Sci M307, Columbia, MO 65212, USA. Electronic address: kayest@health.missouri.edu.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Kayes
authors.forename: Helen
authors.initials: H
authors.lastname: Braley-Mullen
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006965:Hyperplasia / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics*; D007376:Interleukin-2 / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D012974:Sodium Iodide; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology* / Q000473:pathology*; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D007371:Interferon-gamma; D012974:Sodium Iodide
keywords: Autoimmunity; IHC; IL-2; Immunohistochemistry; NOD.H-2h4; SAT; SCID; T cell receptor; T regulatory Cells; TCR; TEC; TEC H/P; Thyroid; interleukin-2; severe combined immunodeficient; spontaneous autoimmune thyroiditis; thyroid epithelial cell; thyroid epithelial cell hyperplasia/proliferation