Evidence for selective accumulation of intrathyroidal T lymphocytes in human autoimmune thyroid disease based on T cell receptor V gene usage

• Published in: The Journal of clinical investigation 1992, Vol.89 (1), p.157-162
• Main Authors: DAVIES, T. F, MARTIN, A, CONCEPTION, E. S, GRAVES, P, LAHAT, N, COHEN, W. L, BEN-NUN, A
• Format: Article
• Language: English
• Subjects: Autoantibodies - immunology; Autoimmune Diseases - immunology; Base Sequence; Biological and medical sciences; Blotting, Southern; Endocrinopathies; Gene Amplification; Graves Disease - immunology; Humans; Leukocytes, Mononuclear - immunology; Lymphocyte Culture Test, Mixed; Medical sciences; Molecular Sequence Data; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oligonucleotides; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; Ribonucleotides; T-Lymphocyte Subsets - immunology; Thyroid Diseases - immunology; Thyroid Neoplasms - immunology; Thyroid. Thyroid axis (diseases); Thyroiditis, Autoimmune - immunology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI115556

We have investigated the T cell receptor V alpha and V beta gene family usage by T lymphocytes infiltrating affected thyroids in patients with autoimmune thyroid disease. We show that the intrathyroidal T lymphocytes from patients (n = 6) with autoimmune thyroid disease display a widespread usage of V beta gene families with an average of 14.4/19 V beta gene families similar to the peripheral T lymphocytes of the same patients. Because we recently reported that the utilization of V alpha gene families is markedly reduced within these mitogen-stimulated intrathyroidal T cell populations, as well as within intact tissue from similar patients (n = 4) (overall mean of 4.0/18 families detected), these results indicate that in thyroids of patients with autoimmune thyroid disease the lymphocytes are selectively accumulating based on their V alpha rather than V beta elements. This preferential hTcR V alpha and widespread V beta gene usage was not mimicked in most 7-d autologous mixed lymphocyte reactions using non-T cell stimulators (n = 6) or EB-virus immortalized autologous B cell lines (n = 3). Hence, the selective V gene utilization by intrathyroidal T cells is likely to be secondary to multiepitopic thyroidal autoantigens activating thyroid infiltrating T cells or to the presence of a superantigenlike thyroidal self-antigen, capable of determining a selective infiltration or activation of a variety of T lymphocytes on the basis of their V alpha gene usage.