Decrease of Intrathyroidal CD161+V.ALPHA.24+V.BETA.11+ NKT Cells in Graves' disease

Abstract

Abstract. To clarify changes in the intrathyroidal natural killer T (NKT) cell subset, which prevents autoimmunity in patients with Graves' disease (GD), we examined intrathyroidal and peripheral lymphocytes in 11 patients with GD and peripheral lymphocytes in nine healthy volunteers using three-color flow cytometry. The proportion of CD161 + T cell receptor Vα24 + Vβ11 + cells, which represent the NKT cell subset, was lower in the thyroid of patients with GD than in the peripheral blood of the same patients and in the peripheral blood of healthy subjects. These results indicate that the proportion of intrathyroidal NKT cells is decreased in patients with GD and that this decrease may contribute to incomplete regulation of autoreactive T cells in GD.

Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment

“…In a second case report, a patient with HCV infection and negative anti-thyroid Abs before treatment but with the typical association for HT (HLA-DR5 antigen or HLA-DRB1.11/HLA-DRB1.12 alleles) in Caucasian developed HT during a-IFN treatment [82] . In a preliminary longitudinal (range 12-54 mo) controls (2%-4%) [11,66] . The standard antiviral therapy with a-IFN for HCVrelated chronic hepatitis may exacerbate or induce underlying latent thyroid disorders, increasing the incidence of AITD and dysfunction to 20%-40% and 11%-15%, respectively [49,[61][62][63]65,67,68,[70][71][72] .…”

“…Specific Tg peptides (representing major T-cell epitopes that can bind to the HLA-DRB-Arg74 pockets) and intron 1 polymorphism in the TSH-r gene (altering its splicing) has been associated with GD [40,41] . Cytotoxic CD8 + T cells recognized Tg or TPO peptide epitopes associated to HLA-A2 molecules in patients with HT [11] . Epigenetic modifications (including DNA methylation, histone modifications, and RNA interference by microRNA) can amplify a risk conferred by an inherited polymorphism resulting in a combined high risk for disease [42] .…”

“…Moreover, HCV also replicates within the infected human thyroid cells in vitro [98] . The HCV infection of thyroid cells can trigger the autoimmune thyroiditis by induction of changes in self Ag expression, exposing of cryptic epitopes or molecular mimicry and leading to production of the proinflammatory IL-8 (a contributor to bystander activation) [11] . Even if important host effector molecules (such as the interferon-induced transmembrane proteins IFITM family of proteins) may act against HCV in the liver, restricting infection by targeting the endocytosed virion for lysosomal degradation [99] , at the moment, no data in the literature describe the role of IFITM in AITD.…”

“…a-IFN triggers AITD through an epigenetic mechanism involving variant of Tg and TSHr gene promoter [101,102] . Moreover, a-IFN locally enhances the expression of TSH-r, Tg, TPO and HLA class Ⅰ molecules on thyrocytes and the secretion of the potent proinflammatory IL-2 cytokine [11] . a-IFN treatment for HCV-related chronic hepatitis acts an enhancer of AITD in susceptible patients.…”

“…T cells CD4 + are divided into regulatory T (Treg) cells and conventional T helper (Th) cells (with Th1 and Th2 lineages controlling cell-mediated and humoral immunity, respectively) [7][8][9][10][11] . In the central event of the immune response, the antigen-presenting cell (APC) presents the Ag bound to the human leukocyte antigen (HLA) class Ⅱ to the CD4 + T cell, through the T cell receptor and additional costimulations (engagement of B7 with CD28 and CD40 with CD40 ligand).…”