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Thyrocytes Responding to IFN- Are Essential for Development of Lymphocytic Spontaneous Autoimmune Thyroiditis and Inhibition of Thyrocyte Hyperplasia¹

Shiguang Yu^*, Gordon C. Sharp^*, and Helen Braley-Mullen^2,*,,

^* Department of Internal Medicine, Department of Pathology, and Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212; and Department of Veterans Affairs, Research Service, Columbia, MO 65212

IFN- 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- promotes L-SAT and inhibits TEC H/P are unknown. To determine whether responsiveness of lymphocytes or thyrocytes to IFN- is important for the development of these lesions, IFN-R^–/– mice, which develop TEC H/P similar to IFN-^–/– 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-^–/–, but not IFN-R^–/– recipients. IFN-R^–/– recipients of WT cells developed severe TEC H/P, but did not develop L-SAT, suggesting that thyrocytes responding to IFN- are important for inhibition of TEC H/P. Unexpectedly, IFN-R^–/– splenocytes or bone marrow did not induce L-SAT in IFN-^–/– or WT mice even though IFN-R^–/– lymphocyte donors produced as much IFN- as lymphocytes from WT donors, and thyrocytes could respond to IFN-. Real-time PCR indicated that recipients of IFN-R^–/– bone marrow expressed less mRNA for IFN--inducible chemokines compared with recipients of WT bone marrow. This might limit the migration of IFN-R^–/– lymphocytes to thyroids. Few IFN-R^–/– lymphocytes infiltrated thyroids even in the presence of WT lymphocytes, suggesting that lymphocytes unable to respond to IFN- are not induced to migrate to thyroids. These results suggest that thyrocytes must be able to respond to IFN- for the development of L-SAT and inhibition of TEC H/P, and lymphocytes must be able to respond to IFN- to induce L-SAT.

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