Adoptive transfer of antithyrotropin receptor (TSHR) autoimmunity from TSHR knockout mice to athymic nude mice

Endocrinology
Mami NakaharaYuji Nagayama

Abstract

We have recently shown that wild type mice are highly tolerant, whereas thyrotropin receptor (TSHR) knockout (KO) mice are susceptible to immunization with the mouse TSHR, the autoantigen in Graves' disease. However, because TSHR KO mice lack the endogenous TSHR, Graves-like hyperthyroidism cannot be expected to occur in these mice. We therefore performed adoptive transfer of splenocytes from TSHR KO mice into nude mice expressing the endogenous TSHR. Anti-TSHR autoantibodies were detected in approximately 50 % recipient mice 4 wk after adoptive transfer of splenocytes (5 × 10⁷/mouse) from TSHR KO mice immunized with adenovirus expressing mTSHR A subunit and persisted for 24 wk. Depletion of regulatory T cells by anti-CD25 antibody in the donor mice increased successful transfer rates without increasing antibody levels. Some recipient mice showed transient increases in thyroid-stimulating antibodies and T₄ levels 4-8 wk after transfer, but many became thyroid-blocking antibody positive and hypothyroid 24 wk later. Adoptive transfer of splenocytes from naïve TSHR KO mice transiently induced very low antibody titers when the recipient mice were treated with anticytotoxic lymphocyte antigen 4 and antiprogrammed cell death 1 ligand...Continue Reading

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Citations

Jul 26, 2012·Thyroid : Official Journal of the American Thyroid Association·Sandra M McLachlanBasil Rapoport
Jul 17, 2015·Current Opinion in Endocrinology, Diabetes, and Obesity·Yuji NagayamaNorio Abiru
Oct 5, 2013·Endocrine Reviews·Sandra M McLachlan, Basil Rapoport
Jun 18, 2017·Frontiers in Immunology·Ralf J LudwigFalk Nimmerjahn
Jul 4, 2020·Nature Reviews. Disease Primers·Terry F DaviesGeorge J Kahaly
Aug 22, 2021·Journal of Endocrinological Investigation·E J Neag, T J Smith

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