Clonal Analysis of T Lymphocytes Infiltrating the Thyroid Gland in Hashimoto’s Thyroiditis

Bagnasco, Marcello; Ferrini, Silvano; Venuti, D.; Prigione, Ignazia; Torre, Giancarlo; Biassoni, Roberto; Canonica, Giorgio Walter

doi:10.1159/000234179

Cited by 36 publications

(9 citation statements)

References 18 publications

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“…In this patient group higher numbers of cytotoxic CD8+ cells (27,28), NK cells (29), and perforin+ cells (30) were detected within thyroid-derived lymphocytes. Patients with HT, but not GD, showed an increased secretion of tumor necrosis factor (TNF)-a from thyroid-derived cell clones (31) and a high level of cytotoxic autoantibodies in the GD,,,»,, Competitive RT-PCR for IL-4, IL-10, IL-2, and IFN-mRNAs in human thyroid tissues.…”

Section: Discussionmentioning

confidence: 65%

Different Cytokine mRNA Profiles in Graves' Disease, Hashimoto's Thyroiditis, and Nonautoimmune Thyroid Disorders Determined by Quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)

Heuer¹,

Aust²,

Ode-Hakim³

et al. 1996

Thyroid

132

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Intrathyroidal lymphocytes are a source of cytokines thought to stimulate or maintain the immune process within the thyroid in Graves' disease (GD) and Hashimoto's thyroiditis (HT). Quantitative assessment of the cytokine profile may provide important clues as to the Th1/Th2 balance prevailing in these diseases. We analyzed cytokine mRNA expression levels in thyroid tissue samples from 13 patients with GD, 2 with HT, 5 with nontoxic multinodular goiter (NTG), and 4 with thyroid autonomy (nodular = TAnod and perinodular = TAperi tissue) using multispecific competitor fragments with primer sequences for IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-gamma, CD25, and CD3 delta-chain mRNA. Patients with GD were subdivided into two groups according to their serum levels of antibodies to thyroperoxidase (anti-TPO; GDhigh > 4000 U/mL, GDlow < or = 200 U/mL). These levels correlated positively with the CD3 delta-chain mRNA levels (r = 0.83) and with the T cell infiltration (r = 0.71) as determined by immunohistochemistry. Patients with GDhigh demonstrated 2- to 4-fold higher IL-4 mRNA levels (as compared to all other investigated groups) and significantly higher IL-10 mRNA levels as compared to HT, GDlow, and TAnod patients. Patients with GDhigh also had significantly higher levels of IFN-gamma, IL-1 beta, IL-8, and CD25 mRNA as compared to GDlow. The highest IFN-gamma, IL-2, and CD25 mRNA levels were found in HT. The lowest mRNA levels of all the investigated groups were detected in TAnod. No significant differences in IL-6 and IL-8 mRNA levels were found between most of the patient groups. In summary, patients with GDhigh showed a shift to a more Th2-driven cytokine pattern. In contrast, the increase mRNA levels of Th1-related cytokines found in HT indicate predominantly T cell-mediated cytotoxic processes.

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Section: Discussionmentioning

confidence: 65%

Different Cytokine mRNA Profiles in Graves' Disease, Hashimoto's Thyroiditis, and Nonautoimmune Thyroid Disorders Determined by Quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)

Heuer¹,

Aust²,

Ode-Hakim³

et al. 1996

Thyroid

132

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“…Furthermore, most cytotoxic T cells are CD8 cells. In fact, cional analysis of intrathyroidal lymphocytes in Hashimoto's disease showed many CD3 ' CD4 CD8 ' cells with NK activity (probably yd TCR' T cells) [26,27] and autoreactive CD8 cells, some of which were thyroid-specific cytotoxic Tcells [28]. Furthermore, an increase of intrathyroidal yS TCR' T cells [29] and activation of intrathyroidal CD8 and CD57 cells [30] were also found in Hashimoto's disease.…”

Section: Discussionmentioning

confidence: 99%

Decreases in αβ T cell receptor negative T cells and CD8 cells, and an increase in CD4 +CD8+ cells in active Hashimoto's disease and subacute thyroiditis

Iwatani

Amino

Hidaka

et al. 1992

Clinical and Experimental Immunology

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SUMMARY We examined peripheral lymphocyte subsets in patients with autoimmune thyroid disease, or subacute thyroiditis, in the active stage when possible. During destructive thyrotoxicosis arising from aggravation of Hashimoto's thyroiditis, both the numbers and proportions of αβ T cell receptor (TCR) negative T (WT31− CD3+) cells and CD8 (CD4− CD8+) cells decreased and those of CD4+ CD8+ cells increased slightly, resulting in proportional increases in CD4 (CD4+ CD8−) cells. non‐T, non‐B (CD5− CD19−) cells, and the CD4/CD8 cell ratio. Changes were similar in active subacute thyroiditis. During stimulative thyrotoxicosis in active Graves' disease, the numbers of such T lymphocyte subsets were not changed, but only the number of CD5+ B (CD5+CD19+) cells increased markedly, resulting in proportional decreases in total T (CD3+) cells, αβ+ TCR T (WT31+ CD3+) cells, CD8 cells, and non‐T, non‐B cells. A serial study of some of the patients showed opposite changes in αβ TCR− T cells, the CD4/CD8 cell ratio, and CD5+ B cells between the active stages of Graves' and Hashimoto's diseases. αβ TCR− T cells were mostly γδ TCR+ T (IIF2+ CD3+) cells in these patients. These data suggest that αβ TCR T (γδTCR+ T), CD8, and CD4+ CD8+ cells are important in thyroid destruction in Hashimoto's disease and subacute thyroiditis, and that CD5+ B cells arc important in thyroid stimulation in Graves' disease.

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“…These molecules, produced by both the infiltrating inflammatory cells and the TFC in autoimmune thyroid disease (Bagnasco et al 1987, Del Prete et al 1989, Zheng et al 1992, Watson et al 1995, Ajjan et al 1996, can induce immunological changes in TFC in addition to affecting their growth and function (Todd et al 1985, Weetman & Rees 1988, Tandon et al 1992, Vargas et al 1994, Tominaga et al 1991, Huber & Davies 1990, Rasmussen et al 1994, Pang et al 1993. Previous studies have shown that cytokines can modulate iodide uptake of TFC by mechanisms that remain unclear (Pang et al 1993, Rasmussen et al 1994.…”

Section: Introductionmentioning

confidence: 99%

The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity

Ajjan

Watson²,

Findlay³

et al. 1998

Journal of Endocrinology

105

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Iodide concentration by the thyroid gland, an essential step for thyroid hormone synthesis, is mediated by the Na + /I symporter (NIS). To identify factors that may regulate this process, we have studied NIS gene expression in the Fisher rat thyroid cell line (FRTL-5) by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique. Increasing concentrations of bovine TSH (0·1, 1, 10, 50 and 100 mU/l), with or without tumour necrosis factor-(TNF ), interferon-(IFN ) or interleukin-1 (IL-1 ) were added to FRTL-5 cells previously deprived of TSH for a minimum of 5 days. RNA was extracted and samples were studied for NIS expression. TSH enhanced NIS mRNA expression in a dose-dependent manner, with induction evident at 0·1 mU/l, reaching a peak at 50 mU/l, an effect detected after 6 h of stimulation, but not in the first 2 h. Both TNF and, to a lesser extent, IL-1 inhibited basal and TSH-induced NIS expression. High concentrations of IFN also downregulated TSH-stimulated NIS mRNA expression.Using the same technique, we also investigated NIS mRNA tissue distribution in two male and one female Wistar rats. High levels of NIS expression were detected in the thyroid, stomach, and mammary gland, lower levels were found in the intestine, adipose tissue and liver, borderline levels were expressed in the salivary gland, and no expression was detected in the kidneys.In summary, we have shown that TSH upregulates rat NIS gene expression in vitro, and this induction can be modulated by cytokines. Analysis of the distribution of rat NIS mRNA ex vivo demonstrated variable levels of NIS transcription in different tissue samples.

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Clonal Analysis of T Lymphocytes Infiltrating the Thyroid Gland in Hashimoto’s Thyroiditis

Cited by 36 publications

References 18 publications

Different Cytokine mRNA Profiles in Graves' Disease, Hashimoto's Thyroiditis, and Nonautoimmune Thyroid Disorders Determined by Quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)

Different Cytokine mRNA Profiles in Graves' Disease, Hashimoto's Thyroiditis, and Nonautoimmune Thyroid Disorders Determined by Quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)

Decreases in αβ T cell receptor negative T cells and CD8 cells, and an increase in CD4 +CD8+ cells in active Hashimoto's disease and subacute thyroiditis

The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity

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