Evidence of limited variability of antigen receptors on intrathyroidal T cells in autoimmune thyroid disease.
BACKGROUND
Patients with autoimmune thyroid diseases, including Graves' disease and Hashimoto's disease, have marked lymphocytic infiltration in their thyroid glands. We examined the gene for the variable regions of the alpha-chain of the human T-cell receptor (the V alpha gene) in intrathyroidal T cells to determine whether the infiltration is a secondary heterogeneous immune response or a more restricted, and therefore primary and presumably pathogenetic, reaction to thyroid autoantigens.


METHODS
We used the polymerase chain reaction to detect small numbers of T cells expressing the variable region of the V alpha gene. Different oligonucleotides were used to amplify complementary DNA for the 18 known families of the V alpha gene in intrathyroidal T cells from 9 patients with autoimmune thyroid disease. We compared the findings with the results in patients with nonautoimmune thyroid disease as well as those in normal subjects.


RESULTS
We found marked restriction in the expression of T-cell-receptor V alpha genes by T cells from the thyroid tissue of patients with autoimmune thyroid disease. An average of only 5 of the 18 V alpha genes were expressed in such samples, as compared with 17 V alpha genes expressed in peripheral-blood T cells from the same patients. No such restriction was found in thyroid tissue from patients with nonautoimmune thyroid disease. The predominantly expressed V alpha genes differed from patient to patient, however, with no clear association with the type of disease.


CONCLUSIONS
Intrathyroidal T-cell accumulation in autoimmune thyroid disease is highly restricted and points to the primacy of T cells in causing thyroid disorders. These results present the possibility of using antibodies to the T-cell receptor for the specific inhibition of abnormal T-cell function in autoimmune thyroid disease.
Davies
T F
TF
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029.
Martin
A
A
Concepcion
E S
ES
Graves
P
P
Cohen
L
L
Ben-Nun
A
A
D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001324:Autoantigens / Q000276:immunology; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D005786:Gene Expression Regulation; D006111:Graves Disease / Q000235:genetics / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000032:analysis; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D017493:Leukocyte Common Antigens; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013601:T-Lymphocytes / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D001324:Autoantigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens