T Cells and Human Autoimmune Thyroid Disease: Emerging Data Show Lack of Need to Invoke Suppressor T Cell Problems

Abstract

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.

p53 codon 72 proline/arginine polymorphism and autoimmune thyroid diseases

“…This suggests that the 53 codon 72 Arg/Pro polymorphism could represent a viable candidate genetic marker for the purpose of predicting the increased susceptibility to the development of HT. HT and GD are both AITD, and undoubtedly, humoral as well as cell-mediated immunity play an important role in the development of both disorders (7,8). It should be recognized, however, that apoptosis also contributes to an individual's susceptibility to AITD, at least partially by way of regulating the maturation and control of the immune response mediated by both T and B lymphocytes (10,11).…”

“…Intrathyroidal lymphocyte infiltration, the pathognomonic feature of AITD, is typically composed of T cells and B cells, implying a contribution to the pathogenesis of both disorders from cell-mediated as well as humoral immunity (7). Typically such B cells are able to produce Abs, such as AMA and antithyroglobulin Ab (ATA), and TRAb (1,3).…”

Has the Use of Antithyroid Drugs for Graves' Disease Become Obsolete?

“…Other workers (48) make convincing arguments against the former suppressor cell defect theory, suggesting that in the absence of definitive prospective studies with functional assessments, the observed cell changes reflect only a nonthyroidal nonspecific immune response. They further emphasize the role of cytokines derived from cells as modify¬ ing the immune response, through effects on either or cells or thyrocytes (48,49). Most investigators do agree that cells play a primary role in the autoimmune process leading to thyroid disease, with cell-mediated cytotoxic thyrocyte destruction in Hashimoto's disease and a more complex series of events appearing in Graves' disease.…”

Lack of association between interleukin-4 gene polymorphisms and autoimmune thyroid diseases amongst Taiwanese Chinese

“…Clinically, active GD patients virtually always appear hyperthyroid, whereas HT patients may be euthyroid, hypothyroid, or occasionally, hyperthyroid. Although the histopathological appearance of both disorders are different in some ways, the thyroid glands of patients suffering from each disorder all present with a rather diffuse cellular infiltration, which is composed of T-and B-cells and other inflammatory cells (especially macrophages), this suggesting the contribution of cell-mediated immunity, as well as humoral immunity, to the pathogenesis of these two diseases [1][2][3]. In practice, an abundance of antibodies (Abs) against certain thyroid-specific components, such as thyrotropin receptor, microsome/thyroid peroxidase and thyroglobulin, can be measured from the sera of the majority of individuals afflicted with either GD or HT [4,5].…”