Lymphocytic traffic and homing into target tissue and the generation of endocrine autoimmunity

Abstract

Summary Endocrine autoimmunity is known to be characterized by the presence of specific autoantibodies and from the histopathological point of view by lymphocytic inflitration in the target tissue. The presence of mononuclear cell infiltrates is the pathological hallmark of most endocrine diseases characterized by an autoimmune process directed against antigens expressed on endocrine cells. Infiltrating cells can usually be detected by biopsy or by using other, non‐invasive, techniques. However, in endocrine tissue such as the islets of Langerhans and the adrenal glands it is difficult to perform biopsies and diagnosis of the autoimmune process is dependent mainly upon detection of specific autoantibodies. A crucial aspect of endocrine autoimmunity and of all processes of organ specific autoimmunity is why and how lymphocytes migrate from primary lymphoid tissue to their specific targets. This occurs mainly through contact with specific adhesion molecules which enable lymphocytes to adhere to the endothelial vessels. In close proximity to the target tissue. In this review we discuss the homing of peripheral mononuclear cells into target endocrine tissues and the mediating role of adhesion molecules.

Lymphocyte traffic and homing in autoimmune thyroid disorders

“…Intrathyroidal lymphocytes seem to play a prominent role in the pathogenesis of AITD not only through thyroid antigen recognition, but also mediating important inflammatory effects, such as the release of cytokines (1,2). In addition, studies in circulating populations are also important because immunological disturbances in AITD are not solely limited to the thyroid gland, as the orbit and occasionally the skin can also be affected (1).…”

“…In AITD, the autoimmune process is probably initiated by the activation of autoreactive T cells by an MHC II/self antigen complex and a co-stimulatory signal that enables full activation of T cells (1). T cell activation is followed by the expression of cell surface antigens and cell adhesion molecules that allows the homing of immune cells onto their target organs (1,2). This invited commentary emphasizes the major events regulating lymphocyte traffic in AITD resulting in targeting of circulating lymphocytes to the target organs: the thyroid and the orbit.…”

“…Human autoimmune thyroid disorders (AITD) -Graves' disease (GD) and Hashimoto's thyroiditis (HT) -are characterized by reactivity to self thyroid antigens, which may be expressed as destructive inflammatory or anti-receptor autoimmune diseases (1)(2)(3). In AITD, the autoimmune process is probably initiated by the activation of autoreactive T cells by an MHC II/self antigen complex and a co-stimulatory signal that enables full activation of T cells (1).…”

The effects of CD40- and interleukin (IL-4)-activated CD23+ cells on the production of IL-10 by mononuclear cells in Graves’ disease: the role of CD8+ cells

“…The presence of antibodies against thyroid-specific antigens such as the thyrotrophin (TSH) receptor, thyroid peroxidase (TPO) and thyroglobulin, and T and B cell infiltration in thyroid tissue reflects an autoimmune-based process in Graves' disease [1][2][3][4]. The augmented production of B cell growth factor (BCGF; IL-14) from peripheral and thyroid-infiltrating lymphocytes [5], increased numbers of CD23 + cells [6] and the secretion of sCD23 [7] may participate in B cell activation in Graves' disease.…”

Relationship between CTLA-4 and CD28 Molecule Expression on T Lymphocytes and Stimulating and Blocking Autoantibodies to the TSH-Receptor in Children with Graves’ Disease

“…A significant role has been ascribed to immune cells, such as antigen presenting cells, lymphocyte T, and lymphocyte B (CD19) that produce antibodies. After activation, they shift to the inflamed thyroid gland, thus leading to the production of antibodies against TSH receptors that either stimulate (TSAb) or block (TBAb) the activity of the thyroid gland [6,7,8,9,10,11,12]. …”