Molecular analysis of antigen receptor variable region repertoires in T lymphocytes infiltrating the intrathyroidal and extrathyroidal manifestations in patients with Graves' disease.
To determine whether T cells infiltrating thyroid, orbital and pretibial tissue of patients with Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD) represent a primary immune response that is directed against certain antigenic determinants shared between these involved tissues, we characterized these T cells at the molecular level. T cell antigen receptor (TcR) variable (V) region gene usage in thyroid, orbital, pretibial tissue and peripheral blood mononuclear cells of patients with GD, GO and PTD was assessed using RT-PCR and 22 V alpha and 23 V beta gene-specific oligonucleotide primers, followed by Southern hybridization analysis using TcR C-region-specific, digoxigenin-labelled oligonucleotide probes. In some instances, CDR3- and junctional regions of TcR V beta genes were sequenced. Marked restriction and similarities of V alpha and V beta gene usage were detected in samples derived from patients with active GO and PTD of recent onset. Moreover, sequence analysis of junctional domains of V beta families revealed oligoclonality of some intrathyroidal, orbital and pretibial T cell populations as well as the presence of conserved junctional motifs shared by T cells derived the thyroid gland and the extrathyroidal sites. These data suggest that similar antigenic determinants may be responsible for the recruitment and oligoclonal expansion of T cells both within the thyroid gland and at the involved extrathyroidal sites in Graves' disease.
Heufelder
A E
AE
Department of Internal Medicine, Ludwig-Maximilians-University, Munich, Germany.
Schworm
H D
HD
Wenzel
B E
BE
Garrity
J A
JA
Bahn
R S
RS
D005128:Eye Diseases / Q000209:etiology / Q000276:immunology*; D015329:Gene Rearrangement, T-Lymphocyte; D006111:Graves Disease / Q000150:complications* / Q000276:immunology; D006801:Humans; D009915:Orbit / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012871:Skin Diseases / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology*; D013977:Tibia
D011948:Receptors, Antigen, T-Cell