The expression of T-cell antigen receptor (TCR) Vβ genes in autoimmune thyroid diseases (AITDs) was investigated. RNA was extracted from the thyroid tissue of 23 patients with early-stage Graves' disease, 19 patients with late-stage Graves' disease and 20 patients with Hashimoto's disease. Peripheral blood lymphocytes from patients and 20 normal subjects (controls) were analysed in parallel. AITD was found to be associated with diminished TCR Vβ gene family utilization. In addition, AITDs appeared to select for specific TCR Vβ families. The Vβ3, Vβ5 and Vβ8 families were expressed more frequently in thyroid-infiltrating T-lymphocytes of early-stage Graves' disease than other Vβ gene families. Selective expression was not observed in infiltrating T-lymphocytes obtained from thyroid tissue of patients with late-stage Graves' disease or Hashimoto's disease. Preferentially expressed TCR Vβ gene families may be useful as molecular targets for targeted immunotherapy of AITDs.
OffnerHVandenbarkAA: T cell receptor V genes in multiple sclerosis: Increased use of TCR Vβ8 and TCR Vβ5 in MBP-specific clones. Int Rev Immunol1999; 18: 9–36.
2.
SimoneEDanielDSchlootNGottliebPBabuSKawasakiE: T cell receptor restriction of diabetogenic autoimmune NOD T cell. Proc Natl Acad Sci USA1997; 94: 2518–2521.
3.
IllesZShimamuraMNewcombeJOkaNYamamuraT: Accumulation of V(alpha) 7.2-J(alpha)33 invariant T cells in human autoimmune inflammatory lesions in the nervous system. Int Immunol2004; 16: 223–230.
4.
KumarV: Homeostatic control of immunity by TCR peptide-specific Tregs. J Clin Invest2004; 114: 1222–1226.
5.
MatsumotoY: New approach to immunotherapy against organ-specific autoimmune disease with T cell receptor and chemokine receptor DNA vaccine. Curr Drug Targets Immune Endocr Metabol Disord2005; 5: 73–77.
VandenbarkAAHashimGOffnerH: Immunization with a synthetic T-cell receptor V-region peptide protects against experiment autoimmune encephalomyelitis. Nature1989; 341: 541–544.
8.
Ben-YehudaABar-TanaRLivoffARonNCohenIRNaparstekY: Lymph node cell vaccination against the lupus syndrome of MRL/lpr/lpr mice. Lupus1996; 5: 232–236.
9.
EliasDTikochinskiFrankelGCohenIR: Regulation of NOD mouse autoimmune diabetes by T cells that recognize a TCR CDR3 peptide. Int Immunol1999; 11: 957–966.
10.
ZhangJ: T-cell vaccination for autoimmune diseases: Immunologic lessons and clinical experience in multiple sclerosis. Expert Rev Vaccines2002; 1: 285–292.
11.
Van der AaAHellingNMedearRGelinGPalmersYRausJ: T cell vaccination in multiple sclerosis patients with autologous CSF-derived activated T cells: Results from a pilot study. Clin Exp Immunol2003; 131: 155–168.
12.
MorelandLWMorganEEAdamsonTC3rdFronekZCalabreseLHCashJM: T cell receptor peptide vaccination in rheumatoid arthritis: A placebo controlled trial using a combination of Vβ3, Vβ4, Vβ17 peptides. Arthritis Rheum1998; 41: 1919–1929.
13.
BridgesSLJrMorelandLW: T cell receptor peptide vaccination in the treatment of rheumatoid arthritis. Rheum Dis Clin North Am1998; 24: 641–650.
14.
MaynardJPeterssonKWilsonDHAdamsEJBlondelleSEBoulangerMJ: Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: Insights into MHC bias and antigen specificity. Immunity2005; 22: 81–92.
15.
HeufelderAEHerterichSErnstGBahnRSScribaPC: Analysis of retroorbital T cell antigen receptor variable region gene usage in patients with Graves' ophthalmopathy. Eur J Endocrinology1995; 132: 266–277.
16.
DaviesTFConcepcionESBen-NunAGravesPNTarianG: T cell receptor V gene use in autoimmune thyroid disease: Direct assessment by thyroid aspiration. J Clin Endocrinol Metab1993; 76: 660–666.
17.
KozovskaMFYamamuraTTabiraT: T-T cellular interaction between CD4-CD-regulatory T cells and T cell clones presenting TCR peptide. Its implication for TCR vaccination against experimental autoimmune encephalomyelitis. J Immunol1996; 157: 1781–1790.
18.
SuzukiMChengKCKrugMSYooTJ: Successful prevention of retrocochlear hearing loss in murine experimental allergic encephalomyelitis with T cell receptor Vβ8 specific antibody. Ann Otol Rhinol Laryngol1998; 107: 917–927.
19.
StinissenPZhangJMedaerRVandevyverCRausJ: Vaccination with autoreactive T cell clones in multiple sclerosis: Overview of immunological and clinical data. J Neurosci Res1996; 45: 500–511.
20.
GoldDPSmithRAGoldingABMorganEEDafashyTNelsonJ: Results of a phase I clinical trial of T cell receptor vaccine in patients with multiple sclerosis. II comparative analysis of TCR utilization in CSF T cell populations before and after vaccination with a TCR Vβ6 CDR2 peptide. J Neuroimmunol1997; 76: 29–38.
21.
MusselliCDaverio-ZanettiSZanettiM: Antigenized antibodies expressing Vβ8.2 TCR peptides immunize against rat experimental allergic encephalomyelitis. J Immune Based Ther Vaccines2004; 2: 9–29.
22.
MatsumotoYJeeYSugisakiM: Successful TCR based immunotherapy for autoimmune myocarditis with DNA vaccines after rapid identification of pathogenic TCR. J Immunol2000; 164: 2248–2254.
23.
KumarVMaglioneJThatteJPedersonBSercarzEWardES: Induction of a type 1 regulatory CD4 T cell response following v beta 8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis. Int Immunol2001; 13: 835–841.
24.
MiyakoshiAYoonWKJeeYMatsumotoY: Characterization of the antigen specificity and TCR repertoire, and TCR-based DNA vaccine therapy in myelin basic protein-induced autoimmune encephalomyelitis in DA rats. J Immunol2003; 170: 6371–6378.
25.
WuHWaltersGKnightJFAlexanderSI: DNA vaccination against specific pathogenic TCRs reduces proteinuria in active Heymann nephritis by inducing specific autoantibodies. J Immunol2003; 171: 4824–4829.
26.
InokiTYamagamiSSakaiRIsobeMTsuruTKawashimaH: Suppression of experimental autoimmune uveoretinitis by anti-alphabeta TCR monoclonal antibody. Jpn J Ophthalmol2002; 46: 518–524.
DaviesTFMartinAConcepcionESGravesPCohenWLBen-NunA: Evidence of limited variability of antigen receptors on intrathyroidal T cells autoimmune thyroid disease. N Engl J Med1991; 325: 238–244.
29.
DaviesTFMartinAConcepcionESGravesPLahatNCohenWL: Evidence of selective accumulation of intrathyroidal T-lymphocytes in V gene usage. J Clin Invest1992; 89: 157–162.
30.
McIntoshRSWatsonPFPickerillAPDaviesRWeetmanAP: No restriction of intrathyroidal T cell receptor Vα families in the thyroid of Graves' disease. Clin Exp Immunol1993; 91: 147–152.
31.
McMurrayRWHoffmanRWTangHBraley-MullenH: T cell receptor Vβ usage in murine experimental autoimmune thyroid. Cell Immunol1996; 172: 1–9.
32.
LehmannPVSercarzEEForsthuberTDayanCMGammonG: Determinant spreading and the dynamics of the autoimmune T cell repertoire. Immunol Today1993; 14: 203–208.
33.
NavarreteCBottazoGF: In search of TCR restriction in autoreactive T cell in human autoimmunity: Why is it so elusive?. Clin Exp Immunol1993; 91: 189–192.
