title: Thyrocytes responding to IFN-gamma are essential for development of lymphocytic spontaneous autoimmune thyroiditis and inhibition of thyrocyte hyperplasia.
abstract: IFN-gamma promotes the development of lymphocytic spontaneous autoimmune thyroiditis (L-SAT) in NOD.H-2h4 mice and inhibits the development of thyrocyte hyperplasia and proliferation (TEC H/P). The precise mechanisms by which IFN-gamma promotes L-SAT and inhibits TEC H/P are unknown. To determine whether responsiveness of lymphocytes or thyrocytes to IFN-gamma is important for the development of these lesions, IFN-gammaR-/- mice, which develop TEC H/P similar to IFN-gamma-/- mice, were used as recipients for adoptive cell transfer. Wild-type (WT) splenocytes or bone marrow induced L-SAT and inhibited TEC H/P in IFN-gamma-/-, but not IFN-gammaR-/- recipients. IFN-gammaR-/- recipients of WT cells developed severe TEC H/P, but did not develop L-SAT, suggesting that thyrocytes responding to IFN-gamma are important for inhibition of TEC H/P. Unexpectedly, IFN-gammaR-/- splenocytes or bone marrow did not induce L-SAT in IFN-gamma-/- or WT mice even though IFN-gammaR-/- lymphocyte donors produced as much IFN-gamma as lymphocytes from WT donors, and thyrocytes could respond to IFN-gamma. Real-time PCR indicated that recipients of IFN-gammaR-/- bone marrow expressed less mRNA for IFN-gamma-inducible chemokines compared with recipients of WT bone marrow. This might limit the migration of IFN-gammaR-/- lymphocytes to thyroids. Few IFN-gammaR-/- lymphocytes infiltrated thyroids even in the presence of WT lymphocytes, suggesting that lymphocytes unable to respond to IFN-gamma are not induced to migrate to thyroids. These results suggest that thyrocytes must be able to respond to IFN-gamma for the development of L-SAT and inhibition of TEC H/P, and lymphocytes must be able to respond to IFN-gamma to induce L-SAT.
authors.affiliation: Department of Internal Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors.forename: Shiguang
authors.initials: S
authors.lastname: Yu
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Sharp
authors.forename: Helen
authors.initials: H
authors.lastname: Braley-Mullen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001483:Base Sequence; D018925:Chemokines / Q000235:genetics; D006965:Hyperplasia; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013961:Thyroid Gland / Q000276:immunology* / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000096743:Interferon gamma Receptor
chemical_list: D018925:Chemokines; D007371:Interferon-gamma; D012333:RNA, Messenger; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor