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


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Title: Adoptive transfer of antithyrotropin receptor (TSHR) autoimmunity from TSHR knockout mice to athymic nude mice
Authors: Nakahara, Mami / Johnson, Kristian / Eckstein, Anja / Taguchi, Ryo / Yamada, Masanobu / Abiru, Norio / Nagayama, Yuji
Issue Date: 1-Apr-2012
Publisher: The Endocrine Society
Citation: Endocrinology, 153(4), pp.2034-2042; 2012
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 × 10 7/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 1 antibodies for 8 wk after transfer. Histologically, macrophages infiltrated the retrobulbar adipose tissues and extraocular muscles in a small fraction of the recipients. Our findings demonstrate successful adoptive transfer of anti-TSHR immune response from TSHR KO mice to nude mice. Although the recipient mice developed only transient and infrequent hyperthyroidism, followed by eventual hypothyroidism, induction of orbital inflammation suggests the possible role of anti-TSHR immune response for Graves' orbitopathy.
Keywords: cytotoxic T lymphocyte antigen 4 / nterleukin 2 receptor alpha / programmed death 1 ligand 1 / thyroid stimulating immunoglobulin / thyrotropin receptor / thyrotropin receptor antibody / thyroxine / Adenovirus / adipose tissue / adoptive transfer / animal cell / animal experiment / animal model / animal tissue / antibody detection / antibody titer / article / autoimmunity / cell infiltration / controlled study / endocrine ophthalmopathy / extraocular muscle / female / histopathology / hormone blood level / hyperthyroidism / hypothyroidism / immune response / knockout mouse / macrophage / mouse / nonhuman / nude mouse / orbit inflammation / priority journal / regulatory T lymphocyte / spleen cell / T cell depletion
URI: http://hdl.handle.net/10069/29075
ISSN: 00137227
DOI: 10.1210/en.2011-1846
Rights: Copyright © 2012 by The Endocrine Society.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/29075

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