Intrathyroidal T cell accumulation in Graves' disease: delineation of mechanisms based on in situ T cell receptor analysis.
We have explored the pattern of T cell clonal and nonclonal expansion within the thyroid glands of 7 patients with surgically treated hyperthyroid Graves' disease. Radiolabeled RT-PCRs were performed with 18 V alpha and 21 V beta oligonucleotides as forward primers and 32 P-labeled constant (C) region oligonucleotides as reverse primers, giving 273 experiments in all. Peripheral blood mononuclear cells showed CDR3 banding patterns involving at least 6-12 distinct bands per V gene family. However, 2 distinct banding patterns were seen with intrathyroidal T cell samples. The first was a limited number of bands (< 6), representing within V gene family restriction, seen in 38/153 (25%) PCR positive samples. The second was the presence of markedly enhanced bands representing either clonal expansion or accumulation of T cells using the same V gene with the same CDR3 length and observed in 15/153 (10%) of samples. Further examination of the enhanced bands by sequencing of gel-selected PCR-amplified V gene products showed the presence of both T cell clonal expansion, as evidenced by similar CDR3 sequences, and in a few samples, heterogenous T cell populations, as evidenced by differing CDR3 sequences, yet all sharing the same V gene family. These data support the hypothesis that the human intrathyroidal T cell population in Graves' disease was selected by two distinct mechanisms. The first was associated with the TcR V gene invariant product and represented by nonclonal accumulation of T cells sharing the same V gene. The second mechanism responsible for T cell accumulation was specific antigen recognition by the human T cell receptor CDR3 region and was represented by clonally expanding T cells.
Nakashima
M
M
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Martin
A
A
Davies
T F
TF
D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D015870:Gene Expression; D006111:Graves Disease / Q000473:pathology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D017421:Sequence Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D013961:Thyroid Gland / Q000473:pathology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D012194:RNA-Directed DNA Polymerase