Graves’ disease (GD) and Hashimoto thyroiditis (HT) are classified as autoimmune thyroid disorders (AITD) characterized by the breakdown of self-tolerance to thyroid antigens resulting in circulation of antibodies and lymphocyte infiltration . There is a growing trend for the prevalence of Hashimoto’s disease and it is estimated at approximately 5-10% [2, 3]. Women are diagnosed with it five to ten times more often than men and its frequency increases with the age (the highest number of cases is observed between 45 and 65) . In pediatric population, the most common age at presentation is adolescence’ yet, HT may develop at any time, rarely even in infants [4, 5]. In case of GD, meta-analyses of different studies have estimated the general frequency of the disease to be about 1% . However, Graves’ disease is four to five times more common in women than in men .
The pathogenesis of HT is basically the result of cell-mediated autoimmune, whereas GD results from humoral autoimmunity [8, 9]. However, as in other autoimmune disorders, in AITD, humoral and cellular immune mechanisms are closely connected and cross-linked . Moreover, in both diseases, the thyroid cell itself takes part in the intrathyroidal immune process. Classically, HT is considered to be a Th1-mediated disease’ yet, this classification has altered due to the description of new Th cell subsets including Th17 cells . In accordance with the newest research findings, uncontrolled Th17 cell responses have been involved in different types of autoimmune diseases, which were previously supposed to be Th1-dependent diseases . In HT, as a consequence, chronic inflammatory cell infiltrates into the thyroid gland, which includes predominantly thyroid-specific B and T cells. In result, goiter may initially be caused . Subsequently, hypothyroidism, the characteristic hallmark of thyroiditis, can develop when sufficient numbers of follicular cells responsible for the production and secretion of thyroid hormones thyroxine (T4) and triiodothyronine (T3) are destroyed . It is now well established that GD, B, and T lymphocyte-mediated autoimmunity are known to be directed against four well-known thyroid antigens: thyroglobulin (Tg), thyroid peroxidase (TPO), sodium-iodide symporter (NIS) and the thyrotropin receptor (TSH-R) [15, 16]. However, the THS-R itself is the main autoantigen of GD . The circulating agonist autoantibodies against the TSH-R (TRAb), which bind to and activate the receptor, they, thereby, chronically stimulate thyroid hormone synthesis and secretion (causing hyperthyroidism) as well as thyroid hyperplasia and (causing a diffuse goiter) . Furthermore, TRAb, particularly in children, strongly stimulate thyroid function and have prognostic significance, probably as costimulatory molecules [19, 20]. Thyroid-associated ophthalmopathy occurs in around 25% of cases and is the most common extrathyroidal manifestation of GD [21, 22]. Furthermore, both the humoral and cellular immune actions seem to be present in its pathogenesis .
The majority of researchers share the opinion that AITD are multifactorial diseases, caused by a complex interplay of genetic, hormonal, and environmental influences that provoke the development of inappropriate immune responses against thyroid on multiple levels and the initiation of a long-standing autoimmune reaction [23–25]. This review will focus on the role of the T regulatory (Treg) and T helper (Th) (especially Th17) lymphocytes, and also of B lymphocytes in AITD pathogenesis. However, we have much more to learn about cellular mechanisms and interactions in AITD before we can develop complete understanding of AITD pathophysiology.