Evidence of a Combined Cytotoxic Thyroglobulin and Thyroperoxidase Epitope-Specific Cellular Immunity in Hashimoto's Thyroiditis

Ehlers, Margret; Thiel, Anne; Bernecker, C.; Porwol, Dominika; Papewalis, Claudia; Willenberg, Holger S.; Schinner, Sven; Hautzel, Hubertus; Scherbaum, Werner A.; Schott, M.

doi:10.1210/jc.2011-2178

Cited by 66 publications

(58 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although it was suggested that HT may mainly result from local autoimmune mechanisms in the thyroid gland [12,13], changes in the peripheral T cell distribution were detected in our study. Our results demonstrated a significant increase of CD28-negative T cells in HT patients, associated with CMV-seropositivity within the CD8+ T cell subpopulation.…”

Section: Discussioncontrasting

confidence: 77%

See 1 more Smart Citation

Lower CD28+ T cell proportions were associated with CMV-seropositivity in patients with Hashimoto’s thyroiditis

et al. 2013

View full text Add to dashboard Cite

BackgroundAlterations in the naive T cell subpopulations have been demonstrated in patients with T cell mediated autoimmune disorders, reminiscent of immunological changes found in the elderly during immunosenescence, including the switch from CD45RA + to CD45RO + T cells and decreased thymic function with increased compensatory proliferative mechanisms, partly associated with latent Cytomegalovirus (CMV) infection. The present study was aimed to investigate proportions of lymphocytes, their relation to CMV-seropositivity and the replicative history of CD45RA + expressing T cells in Hashimoto’s thyroiditis (HT, n = 18) and healthy controls (HC, n = 70).MethodsProportions of peripheral T cells were investigated by flow cytometry. The replicative history was assessed by T cell receptor excision circles (TRECs) and relative telomere length (RTL). Expression of CD62L was analyzed by immunohistochemistry in thyroid sections. The role of CMV was assessed by serology, ELISPOT assay and in situ hybridization.ResultsOur results demonstrated a significant increase of CD28-negative T cells, associated with CMV-seropositivity in HT patients. HT showed abundant CD45RO + T cells with peripheral loss of CD62L-expressing CD8 + CD45RA + T cells, the latter mainly depending on disease duration. CD62L was expressed in thyroid lymphocyte infiltrations. The diagnosis of HT and within the HT group CMV-seropositivity were the main determinants for the loss of CD28 expression. RTL was not different between HC and HT. HT showed significantly lower TRECs in CD4 + CD45RA + T cells compared to HC.ConclusionsPatients with HT display a peripheral T cell phenotype reminiscent of findings in elderly persons or other autoimmune disorders. Whether these mechanisms are primary or secondary to the immunological alterations of autoimmune conditions should be investigated in longitudinal studies which may open research on new therapeutic regimes for treatment of HT and associated autoimmune diseases.

show abstract

Section: Discussioncontrasting

confidence: 77%

“…Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disorder of the thyroid gland associated with diffuse lymphoid infiltration, inflammatory destruction of follicular cells and auto-antibodies against thyroid-specific self-antigens [10-12]. However, the etiopathogenesis of HT is far from being clearly understood [13].…”

Section: Introductionmentioning

confidence: 99%

Lower CD28+ T cell proportions were associated with CMV-seropositivity in patients with Hashimoto’s thyroiditis

et al. 2013

View full text Add to dashboard Cite

show abstract

“…[58] In the same study Hashimoto's thyroiditis patients showed significantly lower proportions of CD8+ T cells than healthy control. [58] Some authors have demonstrated a significant decrease in all populations of T-lymphocytes in Graves’ disease hyperthyroid patients. [55] These reports are contradictory to our finding of increased peripheral total lymphocytic count in AITDs.…”

Section: Discussionmentioning

confidence: 94%

Immunoregulatory T cells, LFA-3 and HLA-DR in autoimmune thyroid diseases

Nada

Hammouda

2014

Indian J Endocr Metab

View full text Add to dashboard Cite

Aim:The aim of the present study was to examine the changes in the expression of T-cell activation markers, namely CD4+ CD25+ and CD8+ in patients with AITD, namely Graves’ disease and Hashimoto's thyroiditis as well as colloid nodular goitre. HLA-DR, LFA-3, and peripheral total lymphocytic count are also measured.Materials and Methods:We compared the expression of CD4, CD25, and CD8 surface markers in peripheral blood lymphocyte in Graves’ disease and Hashimoto's thyroiditis as autoimmune thyroid diseases, as well as colloid goitre in comparison with healthy controls. Also, LFA-3 and HLA-DR were measured in the same groups using three-color flow cytometry. Total lymphocytic count in peripheral blood, thyroid function tests, antithyroid antibodies were also included in the laboratory investigations. The total number of participants was 65. All were recruited from endocrine clinics in a tertiary care hospital in the southern region of Saudi Arabia. All participants underwent history taking, clinical examination, laboratory workup, and radiological investigations. Neck ultrasound, technecium pertechnetateψψ thyroid uptake, and fine-needle aspiration and cytology (FNAC) of the thyroid were done when indicated. The study was approved by the Hospital Research Isthics Committee and informed consents were obtained from all participants before enrollment in the study.Results:In comparison with thecontrol group, activation markers CD4, CD25, and CD8 were lower in the autoimmune thyroid diseases. Lymphocyte function antigen-3 (CD58) and total lymphocytic count were higher in the AIT diseases whereas HLA-DR was lower than that in the control group. The CD4/CD8 ratio was lower in the AITD compared with the healthy euthyroid subjects. No difference was found between patients with colloid nodular goitre and the healthy control in any of the study variables except for LFA-3 which was significantly higher in the colloid goitre group.Conclusion:Our findings indicate downregulation of CD4+ CD25+ Treg as well as CD8+ T cells in autoimmune thyroid diseases. Downregulation of suppressor T lymphocytes helps initiation, progression, and maintenance of the autoimmune thyroid diseases. Lower HLA-DR and higher CD58 in AITDs indicate their role in the expression of the autoantigen and its escape from the immune surveillance. High levels of LFA-3 in colloid goitre indicate that the autoimmune process needs interacting factors, and not only the high level of LFA-3.

show abstract

“…16,24 Moving from these experiments in mice, the group of Schott recently studied TPO-and Tg epitope- this study supports the view that in HT a combined TPOand T-specific cytotoxic immnune response does occur. 25 In the last few years, evidence was also accumulated supporting the concept that INF-γ inducible chemokines, such as CXCL10, play an important role in the initial stages of thyroid autoimmunity. When stimulated by IFN-γ, thyroid follicular cells secrete CXCL10, which in turn recruits into the thyroid Th1 lymphocytes expressing CXCR3 and secreting IFN-γ, thus establishing a loop which reinforces and maintains the autoimmunity process.…”

Section: Basic Mechanisms In the Development Of Thyroid Autoimmunitymentioning

confidence: 99%

An overview of the pathogenic mechanisms of autoimmune thyroid disorders

Park¹

2014

KMJ

View full text Add to dashboard Cite

<title>Abstract Objectives, recent epidemiologic studies in humans suggest an increased prevalence of thyroiditis associated with the excessive administration of iodine. More than three times of recommended daily intake of iodine was observed among people in North America. These people generally presented higher level of anti-thyroglobulin antibody, anti-thyroperoxidase antibody, serum thyroid-stimulating hormone and exacerbation of lymphocytic infiltration in thyroid, which indicated the overconsumption of iodine could induce hypothyroidism and enhance the autoimmune response. However, the precise mechanism of excessive iodine intake induced autoimmune thyroid disease remains largely unknown.</p><p>Over half a century has elapsed since the 1956 identification of thyroglobulin antibodies and the devising of the first experimental model of autoimmune thyroiditis. Since then an incredible amount of experimental work has led to an ever deeper understanding of the nature of thyroid auto-antigens, the main immune mechanisms responsible for Hashimoto's thyroiditis and graves’ disease, their genetics, and therir environmental risk factor. Yet, in the majority of genetically predisposed people the individual trigger of thyroid autoimmunity remains obscure. Similarly, effective prevention strategies still remain to be established and, hopefully, will be the target of future studies.</p>

show abstract

Evidence of a Combined Cytotoxic Thyroglobulin and Thyroperoxidase Epitope-Specific Cellular Immunity in Hashimoto's Thyroiditis

Abstract: We here report for the first time that both antigens, TPO and Tg, are recognized by CD8-positive T cells and are involved in the thyroid destruction process leading to clinical disease manifestation.

Cited by 66 publications

References 24 publications

Lower CD28+ T cell proportions were associated with CMV-seropositivity in patients with Hashimoto’s thyroiditis

Lower CD28+ T cell proportions were associated with CMV-seropositivity in patients with Hashimoto’s thyroiditis

Immunoregulatory T cells, LFA-3 and HLA-DR in autoimmune thyroid diseases

An overview of the pathogenic mechanisms of autoimmune thyroid disorders

Contact Info

Product

Resources

About