IFN-gamma-deficient mice develop severe granulomatous experimental autoimmune thyroiditis with eosinophil infiltration in thyroids.
To study the role of IFN-gamma in the development of granulomatous experimental autoimmune thyroiditis (EAT), DBA1 mice with a disrupted IFN-gamma gene were used for adoptive EAT induction. Effector cells from either IFN-gamma(+/+) or IFN-gamma(-/-) donor mice activated with mouse thyroglobulin and anti-IL-2R mAb induced severe granulomatous EAT. A predominant infiltration of the thyroid by eosinophils was observed in recipients of IFN-gamma(-/-) effector cells but not in recipients of IFN-gamma(+/+) cells. Compared with wild-type mice, thyroids of recipients of IFN-gamma(-/-) effector cells had decreased expression of mRNA for Th1 cytokines and inducible nitric oxide synthetase. Expression of Th2 cytokine mRNA was comparable to that of IFN-gamma(+/+) mice, and expression of eotaxin was increased in the thyroids of recipients of IFN-gamma(-/-) effector cells. Activation of cells from either IFN-gamma(+/+) or IFN-gamma(-/-) donors in the presence of IL-12 also induced severe granulomatous EAT. Eosinophil infiltration in recipients of IFN-gamma(-/-) cells was unaffected when effector cells were activated with IL-12, and thyroids expressed predominantly Th2 cytokines. The extent of fibrosis of recipient thyroids was generally greater when donor IFN-gamma(+/+) and IFN-gamma(-/-) cells were activated with IL-12. Compared with IFN-gamma(+/+) mice, IFN-gamma(-/-) mice produced lower levels of mouse thyroglobulin-specific autoantibodies after immunization with MTg and LPS. These results indicate that cells from both IFN-gamma(+/+) and IFN-gamma(-/-) donors can induce severe granulomatous EAT. However, damage of thyroid follicles by IFN-gamma(-/-) and that by IFN-gamma(+/+) cells appear to involve different mediators of inflammation.
Tang
H
H
Department of Internal Medicine, University of Missouri-Columbia School of Medicine, 65212, USA.
Sharp
G C
GC
Peterson
K P
KP
Braley-Mullen
H
H
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D016207:Cytokines / Q000235:genetics; D004804:Eosinophils / Q000473:pathology*; D006099:Granuloma / Q000209:etiology*; D007371:Interferon-gamma / Q000172:deficiency / Q000502:physiology*; D018664:Interleukin-12 / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000473:pathology*; D013967:Thyroiditis, Autoimmune / Q000209:etiology* / Q000473:pathology
D001323:Autoantibodies; D016207:Cytokines; D012333:RNA, Messenger; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma; D013954:Thyroglobulin