Costimulatory Molecules and Autoimmune Thyroid Diseases

Salmaso, C.; Olive, Daniel; Pesce, Giampaola; Bagnasco, Marcello

doi:10.1080/08916930290013441

Cited by 47 publications

(31 citation statements)

References 72 publications

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“…Furthermore, CTLA-4 has a role in induction of Th1 response and suppression of Th2 cytokines, an effect that is antagonized by CD28. The balance between CD28 and CTLA-4 expression by T lymphocytes could be a factor in the pathogenesis of autoimmune diseases [28]. In our study, we found an increased percentage of lymphocytes expressing costimulatory molecules with higher detection of the CD28 population on resting and active cells, which is associated with growing dominance of Th2 immune response in the peripheral blood in untreated patients with GD.…”

Section: Discussionsupporting

confidence: 54%

Relationship between CTLA-4 and CD28 Molecule Expression on T Lymphocytes and Stimulating and Blocking Autoantibodies to the TSH-Receptor in Children with Graves’ Disease

Bossowski

Stasiak-Barmuta²,

Urban³

2005

Horm Res Paediatr

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The present study was performed to elucidate the relationship between CTLA-4/CD28 molecules and stimulating (TSAb) and blocking (TBAb) antibodies to the TSH-receptor (TSH-R) in Graves’ disease. CD28 and CD152 (CTLA-4) are glycoprotein molecules which provide a potent costimulatory signal for T-cell activation and proliferation via interactions with their ligands, B7.1/B7.2 molecules, which are present on the surface of antigen-presenting cells. The aim of the study was to estimate the expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4, CD152), CD28, B7.1 (CD80), and B7.2 (CD86) molecules on peripheral blood cells in patients with Graves’ disease (GD) (n = 55, mean age 15.5 ± 5.1 years) and nontoxic nodular goiter (NTNG) (n = 55, mean age 15.2 ± 4.5 years), in comparison with sex and age-matched healthy control subjects (n = 55, mean age 15.2 ± 3.9 years). The expression of the costimulatory molecules on mononuclear cells was analyzed by three-color flow cytometry using a Coulter EPICS XL cytometer. Detection of TSAb and TBAb to the TSH-R using JPO9 CHO cells in unfractionated serum was measured by a highly sensitive commercial radioimmunoassay. When compared with healthy control subjects and euthyroid patients with GD, untreated patients with GD showed a significant increase of CD152+ (p < 0.001, p < 0.001) and CD28+ (p < 0.01, NS) T lymphocytes, respectively. After 6–12 months of methimazole therapy, the percentage of these cells in the peripheral blood of hyperthyroid patients returned to normal values. In addition, patients with GD showed an increase in the percentage of both B7.1 (3.8%) and B7.2 (18.4%) molecules on activated monocytes, compared to patients with NTNG (0.5% p < 0.05, 2.5% p < 0.01, respectively) and healthy control subjects (0.2% p < 0.05, 0.8% p < 0.003, respectively). In patients with untreated GD there was a statistically significant positive correlation between the expression of CTLA-4 on the surface of peripheral blood T cells and the index of TSAb antibodies (R = 0.54, p < 0.001) as well as a negative correlation with TBAb antibody titer (R = –0.58, p < 0.001). However, no such correlations were noted with regard to CD28 and anti-TPO, anti-TG, and TRAb antibodies. We conclude that changes in the expression of costimulatory molecules on the surface of peripheral blood T cells and their significant relationship with the level of antithyroid antibodies indicate an involvement of these molecules in the pathogenesis of GD.

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Section: Discussionsupporting

confidence: 54%

Relationship between CTLA-4 and CD28 Molecule Expression on T Lymphocytes and Stimulating and Blocking Autoantibodies to the TSH-Receptor in Children with Graves’ Disease

Bossowski

Stasiak-Barmuta²,

Urban³

2005

Horm Res Paediatr

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“…This notion led us to the hypothesis that the blockade of CD29 activation could therefore be a therapeutic target for the suppression of relevant diseases (Salmaso et al 2002). By this logic, we established quantitative screening models to develop novel CD29 functional regulators, using specific agonistic antibodies to CD29, other CD29-associated adhesion molecules, such as CD147 and CD98 (Cai et al 2005;Cho et al 2001;Tsurudome and Ito 2000), and matrix protein fibronectin (FN) to functionally activate CD29 in U937 cells (Cho 2008;Cho et al 2001Cho et al , 2004.…”

Section: Introductionmentioning

confidence: 99%

Cell-permeable ceramides act as novel regulators of U937 cell–cell adhesion mediated by CD29, CD98, and CD147

Lee

Cho

2010

Immunobiology

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“…In their hypothesis, thyroid cells in autoimmune thyroid diseases aberrantly express MHC class II antigen and, as non-professional antigen-presenting cells, present thyroid-specific autoantigens to naïve T cells, leading to thyroid autoimmune reaction. However, the lack of expression of costimulatory molecules B7 on thyrocytes [27] suggests induction of tolerance rather than immunity [28]. More recently, thyroid-specific MHC class II transgenic mice did not spontaneously develop autoimmune thyroid disease [29,30].…”

Section: Implications Of Animal Models In Disease Pathogenesismentioning

confidence: 99%

Animal Models of Graves' Hyperthyroidism

Nagayama

2005

Endocr J

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Abstract. Graves' disease is a common organ-specific autoimmune disease characterized by overstimulation of the thyroid gland with agonistic anti-thyrotropin (TSH) receptor autoantibodies, which leads to hyperthyroidism and diffuse hyperplasia of the thyroid gland. Several groups including us have recently established several animal models of Graves' hyperthyroidism using novel immunization approaches, such as in vivo expression of the TSH receptor by injecting syngeneic living cells coexpressing the TSH receptor, the major histocompatibility complex (MHC) class II antigen and a costimulatory molecule, or genetic immunization using plasmid or adenovirus vectors coding the TSH receptor. This breakthrough has made it possible for us to study the pathogenesis of Graves' disease in more detail and has provided important insights into our understanding of disease pathogenesis. The important new findings that have emerged include: (i) the shed A subunit being the major autoantigen for TSAb, (ii) the significant role played by dendritic cells (DCs) as professional antigen-presenting cells in initiating disease development, (iii) contribution of MHC and particularly non-MHC genetic backgrounds in disease susceptibility, and (iv) influence of some particular infectious pathogens on disease development. However, the data regarding Th1/Th2 balance of TSH receptor-specific immune response or the association of Graves' hyperthyroidism with intrathyroidal lymphocytic infiltration are rather inconsistent. Future studies with these models will hopefully lead to better understanding of disease pathogenesis and help develop novel strategies for treatment and ultimately prevention of Graves' disease in humans.

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Costimulatory Molecules and Autoimmune Thyroid Diseases

Cited by 47 publications

References 72 publications

Relationship between CTLA-4 and CD28 Molecule Expression on T Lymphocytes and Stimulating and Blocking Autoantibodies to the TSH-Receptor in Children with Graves’ Disease

Relationship between CTLA-4 and CD28 Molecule Expression on T Lymphocytes and Stimulating and Blocking Autoantibodies to the TSH-Receptor in Children with Graves’ Disease

Cell-permeable ceramides act as novel regulators of U937 cell–cell adhesion mediated by CD29, CD98, and CD147

Animal Models of Graves' Hyperthyroidism

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