Antigen receptor variable region repertoires expressed by T cells infiltrating thyroid, retroorbital, and pretibial tissue in Graves' disease

To date, it has remained unclear whether T cells infiltrating
thyroid, retroorbital, and pretibial tissue of patients with
Graves' ophthalmopathy and pretibial dermopathy represent a primary
immune response that is directed against certain antigenic
determinants shared among these involved tissues. To characterize
these T cells at the molecular level, we compared the T cell
antigen receptor (TcR) variable (V) region gene usage in thyroid,
retroorbital, pretibial tissue, and peripheral blood mononuclear
cells of two patients with Graves' disease, ophthalmopathy, and
pretibial dermopathy. Ribonucleic acid was extracted, reverse
transcribed, and amplified using the PCR and 22 V alpha and 23 V
beta gene-specific oligonucleotide primers. The resulting TcR V
alpha and V beta transcripts were verified by Southern
hybridization analysis using TcR C region-specific,
digoxigenin-labeled oligonucleotide probes. In addition,
complementarity determining regions 3 and junctional regions of TcR
V beta genes were sequenced. Marked similarities of intrathyroidal,
retroorbital, and pretibial TcR V alpha and V beta gene repertoires
were noted with respect to the degree of TcR V gene restriction and
the patterns of individual V genes expressed. Sequence analysis of
junctional domains of V beta families revealed oligoclonality of
intrahyroidal, retroorbital, and pretibial T cells. In addition,
certain conserved junctional motifs were shared by T cells derived
the thyroid gland and the extrathyroidal sites. Our results suggest
that in the two patients with Graves' disease and extrathyroidal
manifestations studied, similar antigenic determinants may have
contributed to the recruitment and oligoclonal expansion of T cells
both within the thyroid gland and at the involved extrathyroidal
sites.