Suppressor T Lymphocyte Dysfunction Is Important in the Pathogenesis of Autoimmune Thyroid Disease: A Perspective

Over the past decade, there was considerable scepticism regarding the existence, nature, and function of suppressor T (Ts) lymphocytes, particularly antigen-specific Ts lymphocytes. The receptors of putative antigen-specific murine Ts hybrids revealed that most either lacked the T cell receptor β(TCRβ) chain or had failed to properly rearrange them and thus could not make a functional receptor. Moreover, studies of the DNA of sequences of the MHC I-J region (considered an important determinant for suppression) fail to show evidence for a unique open reading frame capable of encoding the I-J restriction element. In addition, no molecular basis for suppression had been characterized. These criticisms have now been satisfactorily resolved and the pendulum is swinging in favor of participation by antigen-specific Ts lymphocytes in immune tolerance. Tslymphocytes have now been cloned and cell lines have been found to be idiotypic-specific. Indeed, specific Ts lymphocytes in the periphery have been shown to prevent the appearance of autoreactivity. It is, therefore, legitimate to consider their control as part of the mechanisms of maintaining the integrity of the immune system. Moreover, all human primary Ts clones and the majority of murine Ts clones have now been shown to rearrange TCR αβ. Tslymphocytes are induced by antigen via antigen-presenting cells (APCs), and may do so in the context of MHC class II antigens, a concept not previously accepted. Moreover, there is now considerable evidence that such cells many well be involved in various autoimmune disease states. Evidence is presented herein that these cells are indeed important in autoimmune endocrine diseases, both insulin-dependent diabetes mellitus as well as autoimmune thyroid disease. The suggestion that the thyroid cell itself may initiate autoimmune thyroid disease, perhaps after an external insult, by expressing HLA molecules and presenting antigen directly to T cells, does not withstand close scrutiny and is unlikely to be the initiating factor. The present author feels that the evidence currently available favors the view that a partial defect in antigen-specific Ts lymphocytes [induced by inadequate antigen presentation to such cells by antigen presenting cells (APCs) consequent to an abnormality of the MHC molecule] may be fundamental to these disorders.