Identification of novel HLA-A0201-restricted T-cell epitopes against thyroid antigens in autoimmune thyroid diseases

Cai, Yun; Xu, Xinyu; Zhang, Zheng; Wang, Ping; Hu, Qingfang; Jin, Yu; Wang, Zhixiao; Liu, Xiaoyun; Yang, Tao

doi:10.1007/s12020-020-02264-x

Cited by 3 publications

(5 citation statements)

References 46 publications

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“…The presence of autoreactive CD8+ T cells in NA-SCH could be attributed to higher levels of TSH, and without studying their phenotype it would be too early to label these DMR+CD8+ T cells as pathogenic. A similar study reported the presence of autoreactive CD8+ T cells recognizing TG and TPO epitopes in anti-TG and anti-TPO antibody-negative subjects [21]. Therefore, these observations support the occurrence of positive cellular immune responses even in the absence of humoral immune responses toward thyroid antigens [20,21].…”

Section: Comparison Of Sch Subjects Based On Bcg Vaccinationsupporting

confidence: 70%

“…A similar study reported the presence of autoreactive CD8+ T cells recognizing TG and TPO epitopes in anti-TG and anti-TPO antibody-negative subjects [21]. Therefore, these observations support the occurrence of positive cellular immune responses even in the absence of humoral immune responses toward thyroid antigens [20,21]. However, we cannot comment on whether this could be attributed to the ‘trained immunity’ imparted by BCG, since we did not assess BCG reactive T cells in these subjects.…”

Section: Discussionmentioning

confidence: 95%

“…A total of 10 6 PBMCs/ml labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) (5 mM) were plated in triplicates in flat bottom 24-well tissue culture plates (BD-Falcon, USA) in Roswell Park Memorial Institute medium (RPMI)-1640 medium supplemented with 0.1% penicillin, streptomycin, 10% fetal calf serum and stimulated with optimized concentration of 30µl BCG (2-8 x 10 6 bacilli/ml) (Serum institute, India) or 2µl antiCD3, anti-CD28 DynabeadsTM (Invitrogen, USA) (positive control) or without any stimulant (negative control) for 96 h at 37 °C in 5% CO2 [20,21]. Post culture, the cells were centrifuged at 200g for 10 minutes, acquired on a flow cytometer (FACS Lyric), and analyzed using FACS Suite (version 1.3) software (BD Biosciences, USA).…”

Section: Methodsmentioning

confidence: 99%

“…A total of 10 [20,21]. Post culture, the cells were centrifuged at 200g for 10 minutes, acquired on a flow cytometer (FACS Lyric), and analyzed using FACS Suite (version 1.3) software (BD Biosciences, USA).…”

Section: Peripheral Blood Mononuclear Cell (Pbmc) Isolation and In-vi...mentioning

confidence: 99%

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Effect of neonatal BCG vaccination on the evolution of Hashimoto’s Thyroiditis

Agrawal,

Basak,

Badal

et al. 2024

Preprint

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Background: Hashimoto thyroiditis (HT) involves the autoimmune destruction of thyrocytes with the presence of anti-thyroid peroxidase (TPO) and/or anti-thyroglobulin (TG) antibodies. In autoimmune diseases, an immunomodulatory role of Bacillus Calmette-Guerin (BCG) vaccination has been reported with decreased autoantibody production and induction of regulatory T cells. We hypothesize that a decline in the efficacy of BCG might be associated with the appearance of HT during adulthood. Methods: Adult subjects with subclinical HT (HT-SCH) (n=39) and non-autoimmune subclinical hypothyroidism (NA-SCH) (n=25) were enrolled along with euthyroid healthy controls (HC) (n=20). The BCG-specific immune responses were determined by the Mantoux test and BCG-induced in-vitro proliferation of peripheral blood mononuclear cells (PBMC). Anti-thyroid cellular immune responses were assessed in subjects with human leukocyte antigen (HLA)-A*02 and HLA-A*24 alleles by determining the frequency of CD8+ T cells recognizing major histocompatibility complex (MHC) dextramers (DMR) carrying TPO-derived peptides, by flow cytometry. Results: The HT-SCH group had a lower rate of Mantoux test reactivity (38.5%) as compared to NA-SCH (64%) and HC subjects (65%) (p=0.047). However, the BCG-induced in-vitro proliferation of PBMC was similar in HT-SCH, NA-SCH, and HC groups. Further, the BCG-vaccinated SCH subjects had lower levels of thyroid stimulating hormone (TSH) (p=0.026). Next, the SCH subjects had higher frequencies of peripheral DMR+ CD8+ T cells as compared to HC subjects (p=0.001). Interestingly, the frequency of peripheral DMR+ CD8+ T cells was significantly higher in HT-SCH than HC subjects (p=0.045). Finally, we observed a positive correlation between the frequency of DMR+CD8+ T cells and TSH levels (r = +0.620, p=0.006). Conclusions: Collectively, our results highlight a complex relationship of neonatal BCG vaccination with the genesis of HT, via modulation of autoimmune responses directed towards thyroid autoantigens.

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Section: Comparison Of Sch Subjects Based On Bcg Vaccinationsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Section: Peripheral Blood Mononuclear Cell (Pbmc) Isolation and In-vi...mentioning

confidence: 99%

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Effect of neonatal BCG vaccination on the evolution of Hashimoto’s Thyroiditis

Agrawal,

Basak,

Badal

et al. 2024

Preprint

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“…Free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH), TgAb, and TPOAb were all measured by chemiluminescence assays (Roche Diagnostics GmbH), while TRAb was tested by RIA (Cisbio Bioassays, France). Reference ranges for adults are TSH, 0.270–4.20 mIU/L; FT3, 3.10–6.80 pmol/L; FT4, 12.0–22.0 pmol/L; TgAb, <115 IU/mL; TPOAb, <34.0 IU/mL; and TRAb, 0-1.50 IU/L [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

The Frequency of Intrathyroidal Follicular Helper T Cells Varies with the Progression of Graves’ Disease and Hashimoto’s Thyroiditis

Cai

Wang

Liu

et al. 2022

Journal of Immunology Research

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Objective. Autoimmune thyroid diseases (AITD), mainly Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are common organ-specific autoimmune diseases characterized by circulating antibodies and lymphocyte infiltration. Follicular helper T (Tfh) cell dysregulation is involved in the development of autoimmune pathologies. We aimed to explore the role of intrathyroidal and circulating Tfh cells in patients with GD and HT. Methods. Ultrasound-guided thyroid fine-needle aspiration (FNA) was conducted in 35 patients with GD, 40 patients with HT, and 22 patients with nonautoimmune thyroid disease (nAITD). Peripheral blood samples were also obtained from 40 patients with GD, 40 patients with HT, and 40 healthy controls. The frequencies of intrathyroidal and circulating Tfh cells from FNA and peripheral blood samples were assessed by flow cytometry. Additionally, the correlations between the frequencies of the Tfh cells and the levels of autoantibodies and hormones or disease duration were analyzed. Results. The frequency of intrathyroidal CD4+CXCR5+ICOShigh Tfh cells was higher in HT patients than in GD patients. Significant correlations were identified between the percentages of circulating and intrathyroidal Tfh cells and the serum concentrations of thyroid autoantibodies, especially thyroglobulin antibodies (TgAb), in AITD. Intrathyroidal CD4+CXCR5+ICOShigh Tfh cells were positively correlated with free triiodothyronine (FT3) in HT patients but negatively correlated with FT3 in GD patients. In addition, HT patients with a longer disease duration had an increased frequency of intrathyroidal CD4+CXCR5+ICOShigh and CD4+CXCR5+PD-1+ Tfh cells. In contrast, in the GD patients, a longer disease duration did not affect the frequency of intrathyroidal CD4+CXCR5+ICOShigh but was associated with a lower frequency of CD4+CXCR5+PD-1+ Tfh cells. Conclusions. Our data suggest that intrathyroidal Tfh cells might play a role in the pathogenesis of AITD and they are potential immunobiomarkers for AITD.

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