Graves' disease: Phenotypic and functional analysis at the clonal level of the T-cell repertoire in peripheral blood and in thyroid

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

doi:10.1016/0090-1229(88)90075-x

Cited by 30 publications

(14 citation statements)

References 21 publications

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“…Conversely, the balance between regulatory and effector T cells has been described as a crucial point [5] . Studies on the functional phenotype of infiltrating T cells gave results that were in part contradictory but, taken together, failed to consistently demonstrate a pronounced Th2 predominance, in contrast to AT [62,64,65] . Thus, explaining the epidemiological observations by suggesting a pathogenetic role of stress in GD, but not in AT, with a stress-induced Th1 to Th2 shift is probably simplistic.…”

Section: How Stress May Contribute To Thyroid Autoimmunity: the Puzzlmentioning

confidence: 99%

Stress and Autoimmune Thyroid Diseases

Bagnasco¹,

Bossert²,

Pesce³

2006

Neuroimmunomodulation

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Autoimmune thyroid diseases (AITD) are the far most common autoimmune disorders, their prevalence in Western countries exceeding 5% of the general population. In the large majority of individual cases the clinical impact of AITD is not severe, however, their widespread diffusion renders them a significant health problem. AITD are heterogeneous in their clinical presentation: the two main forms are autoimmune thyroiditis (AT) and Graves’ disease (GD). Although they probably share, at least in part, a common genetic background and may occur in the same family as well as in the same individual, they are definitely two distinct diseases both in their clinical presentation and their pathophysiology. In fact, AT causes structural thyroid damage (mainly via cell-mediated immune destruction of thyroid follicular cells) which results, as a rule, in functional impairment (hypothyroidism); however, depending on clinical variants, evolution towards hypothyroidism may be very low, or thyroid function impairment occurs after an initial phase of mild thyrotoxicosis due to relatively rapid gland destruction. GD patients have hyperthyroidism, often severe, due to autoantibody-mediated thyrotropin receptor stimulation, with thyroid cell hyperplasia and hyperfunction. Such a functional heterogeneity is a key feature for the clinical management: as a matter of fact, therapy of AITD is mainly therapy of thyroid dysfunction. Moreover, since hyperthyroidism is quite early perceived by the patient as a cause of discomfort, the timing of the natural history of GD is relatively well defined; on the other hand, AT may be asymptomatic for a long time and defining its natural history in a single patient may be difficult. In some AITD patients (mainly, but not exclusively, with GD), clinical features not directly related to thyroid dysfunction, such as orbitopathy, are present. Graves’ orbitopathy is probably related, at least in part, to autoantibodies directed to thyrotropin receptor; it may be, in a minority of patients, severe and sight-threatening, and represents an independent clinical problem.

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Section: How Stress May Contribute To Thyroid Autoimmunity: the Puzzlmentioning

confidence: 99%

Stress and Autoimmune Thyroid Diseases

Bagnasco¹,

Bossert²,

Pesce³

2006

Neuroimmunomodulation

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“…Nevertheless, different methods of detection produced different results as to the numbers of IFN-7-producing cells within the thyroid (14)(15)(16)(17). Because cell clones cannot provide data on the in vivo situation of cytokine secretion, another approach was selected.…”

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confidence: 99%

Activated and interferon-γ producing thyroid-derived T cells are detected in Graves' disease, thyroid autonomy as well as in non-toxic multinodular goiter

Aust

Lehmann

Laue

et al. 1996

European Journal of Endocrinology

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The relative numbers of activated and interferon gamma (IFN-gamma)-producing peripheral blood lymphocytes (PBL) and thyroid-derived lymphocytes (TL) were determined using double surface and intracellular labeling techniques in flow cytometry. Cells were analyzed from 10 patients with Graves' disease (GD), eight patients with thyroid autonomy (TA) and five patients with non-toxic multinodular goiter (NTG). A maximum of 1% IFN-gamma+ cells were detected both in unstimulated PBL and TL. Stimulation caused a two- to threefold higher number of IFN-gamma+ cells in TL (GD, 48 +/- 12%; TA, 48 +/- 11%; NTG, 50 +/- 15%) as compared to PBL (GD, 15 +/- 7%; TA, 16 +/- 8%, NTG, 18 +/- 10%) of the same patients. Nearly all IFN-gamma+ TL in GD were CD3+ T cells, whereas 10-20% of IFN-gamma+ TL in TA and NTG were NK cells. In PBL 80% and in TL almost 100% of IFN-gamma+ cells were antigen-primed CD45RO+ cells. Only 25-35% of IFN-gamma+ thyroid-derived T cells expressed the CD4 antigen. About 42 +/- 10% thyroid-derived T cells in GD, 33 +/- 11% in TA and 34 +/- 13% in NTG expressed the HLA-DR molecule but not the interleukin 2 (CD25) or the transferrin receptor (CD71). Forty per cent of these HLA-DR+ T cells showed an intracellular staining for IFN-gamma and half of them co-expressed the activation antigen CD69. Immunofluorescence double labeling on thyroid cryostat sections demonstrated that HLA-DR+ T cells were also present in situ. The presence of activation antigens on thyroid-derived T cells not only in patients with GD but also in TA and NTG suggests failsafe mechanisms such as anergy, suppression or cytokine regulation in so-called non-immunogenic goiter.

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“…We [3] and Papic et al [23] have reported a reduced production of IL-2 by PHA-induced PBMC from hyperthyroid Graves' patients. An analysis at the clonal level of peripheral blood or intrathyroid T cells from two Graves' patients revealed only about 3O' yr> of the clones to be able to release IL-2, compared with more than 80% in Hashimoto's patients [24]. The IL-2 production defect was restored to normal during antithyroid drug treatment or in remission [3].…”

Section: Discussionmentioning

confidence: 87%

Modulation of the IL-2 production defect in vitro in Graves'disease

Eisenstein

Engelsman

Weiss

et al. 1994

Clinical and Experimental Immunology

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SUMMARYIL-2 production by mitogen-induced peripheral blood mononuclear cells was reported to be reduced in several autoimmune diseases, including Graves" disease (GD). This production defect in hyperlhyroid GD was restored to normal by antithyroid drug therapy or during remission. However, its underlying mechanism and role in the autoimmune process are still uncertain. The present study was undertaken in order to screen ihs in vitro lL-2 generating system for putative factors responsible for its failure, and to see to what extent this was reversible. Thyroid hormone or antithyroid drugs had no effect on lL-2 produciion in vitro. Cultures were found lo be free of soluble inhibitors of IL-2 production or action. IL-1 deficiency as a cause of the IL-2 defect was ruled out; ralher. Graves' adherent cells were found to be activated in being capable of secreting large amounts of IL-1 and prostaglandin E: (PGE;). The latter was noi found to be responsible for ihe decreased lL-2 production, IL-2 production by Graves' mononuclears was completely restored to normal by: (i) adherent cell depletion, irradiation or substitution with normal adherent cells; (ii) preincubation of mononuclears for 24-72 h before mitogen stimulation; (iii) the synergistic action ofa phorbol ester and a calcium ionophore. These data indicate that inhibitionby activated adherent ceils accounts for the in vitro IL-2 produciion defect in GD. Thi.s inhibition is not mediated by soluble factors, but probably through direct interaction with the producing cells, and is reversible in rested cultures or through a bypassed signal Iransduction.

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Graves' disease: Phenotypic and functional analysis at the clonal level of the T-cell repertoire in peripheral blood and in thyroid

Cited by 30 publications

References 21 publications

Stress and Autoimmune Thyroid Diseases

Stress and Autoimmune Thyroid Diseases

Activated and interferon-γ producing thyroid-derived T cells are detected in Graves' disease, thyroid autonomy as well as in non-toxic multinodular goiter

Modulation of the IL-2 production defect in vitro in Graves'disease

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