T cells and human autoimmune thyroid disease: emerging data show lack of need to invoke suppressor T cell problems.
Human T cells recognize self and foreign antigens when such antigens are processed into small peptides and bound to molecules coded for by genes of the HLA region on chromosome 6. The part of the T-cell surface which is responsible for such recognition is a set of molecules coded for by a variety of genes and known as the T-cell-receptor complex. In animal models, T cells are able to transfer autoimmune thyroiditis and T cells have, therefore, long been implicated in the etiology of human autoimmune thyroid disease (AITD). Information gained from the study of intrathyroidal T cells and thyroid antigen-specific T-cell clones has shown that in patients with Graves' disease, mainly helper T-cell clones have been obtained, whereas in autoimmune (Hashimoto's) thyroiditis cytolytic T-cell clones may be predominant. Such thyroid antigen-specific T cells have now been shown to recognize one or other of the three major thyroid-specific antigens; thyroglobulin, thyroid peroxidase, or the TSH receptor and efforts are currently in progress to characterize the T-cell epitopes of these major thyroid autoantigens. Recent findings of restricted T-cell receptor V gene use amongst intrathyroidal T cells confirm the primary role of T cells in human thyroid autoimmune processes leading to AITD. However, the mechanisms whereby such autoreactive T cells escape deletion and anergy, and how they become activated, remain uncertain. There is compelling evidence that the thyroid cell itself, by expressing HLA molecules, and presenting antigen directly to the T cells, may initiate disease, perhaps after an external insult.
Martin
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Department of Medicine, Mount Sinai School of Medicine, New York, New York.
Davies
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D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D000939:Epitopes; D006680:HLA Antigens / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D001324:Autoantigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000939:Epitopes; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell; D016201:Receptors, Lymphocyte Homing