ArticleThyroid : official journal of the American Thyroid Association2009
Thyroid antigens, not central tolerance, control responses to immunization in BALB/c versus C57BL/6 mice.
Article in Thyroid : official journal of the American Thyroid Association, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Nanoparticles Bearing TSH Receptor Protein and a Tolerogenic Molecule Do Not Induce Immune Tolerance but Exacerbate Thyroid Autoimmunity in hTSHR/NOD.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Aberrant Iodine Autoregulation Induces Hypothyroidism in a Mouse Strain in the Absence of Thyroid Autoimmunity.Journal of the Endocrine Society · 2018Article
- Thyroid Autoantibodies Display both "Original Antigenic Sin" and Epitope Spreading.Frontiers in immunology · 2017Review
- Thyrotropin Receptor Epitope and Human Leukocyte Antigen in Graves' Disease.Frontiers in endocrinology · 2016Review
- A unique mouse strain that develops spontaneous, iodine-accelerated, pathogenic antibodies to the human thyrotrophin receptor.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Breaking tolerance to thyroid antigens: changing concepts in thyroid autoimmunity.Endocrine reviews · 2014Review
- P3 mAb: An Immunogenic Anti-NeuGcGM3 Antibody with Unusual Immunoregulatory Properties.Frontiers in immunology · 2012Article
- Antibodies to thyroid peroxidase arise spontaneously with age in NOD.H-2h4 mice and appear after thyroglobulin antibodies.Endocrinology · 2010Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundVaccination with cDNA for the human thyrotropin receptor (TSHR) in a plasmid, without adjuvant, induces TSHR antibodies in C57BL/6 but rarely in BALB/c mice. This outcome could be due to a difference between "high" versus "low" antibody responder mouse strains. However, unlike their poor response to TSHR-DNA vaccination, BALB/c mice vaccinated with thyroid peroxidase (TPO)-cDNA readily develop antibodies to TPO. We hypothesized that insight into these conundrums would be provided by the following differences in central tolerance: (i) between two mouse strains (C57BL/6 versus BALB/c) for the TSHR; and (ii) between two thyroid autoantigens (TPO and the TSHR) in one mouse strain (BALB/c).
methodsWe studied autoantigen expression using real-time polymerase chain reaction to quantify mRNA transcripts for the TSHR, TPO, and thyroglobulin (Tg) in thymic tissue (as well as in thyroid) of young mice.
resultsOur hypothesis was not confirmed. Intrathymic TSHR transcript expression was similar in BALB/c and C57BL/6 mice. Moreover, thymic mRNA transcripts for TSHR and TPO were comparable. Unlike the 10-fold differences for the autoantigens in thyroid tissue (Tg greater than TPO which, in turn was greater than the TSHR), intrathymic transcripts for TPO and the TSHR were similar, both being slightly lower than the level for Tg.
conclusionsCentral tolerance, assessed by measuring intrathymic transcripts of thyroid autoantigens, does not explain the different outcome of TSHR-DNA vaccination in BALB/c and C57BL/6 mice, or even susceptibility versus resistance to hyperthyroidism induced by TSHR-adenovirus. Instead, differences in MHC and TSHR T-cell epitopes likely contribute to TSHR antibody development (or not) following DNA plasmid immunization. The greater immunogenicity of TPO versus TSHR probably relates to the greater number of nonhomologous amino acids in the human and mouse TPO ectodomains (78 amino acids) than in the human and mouse TSHR ectodomains (58 amino acids). Overall, the autoantigens themselves, not central tolerance, control DNA plasmid-induced immunity to TPO and the TSHR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.