title: New aspects of thyroid immunity.
abstract: Like all autoimmune diseases, those affecting the thyroid arise as the result of an interaction between genetic, environmental and endogenous factors. Genes outside the human leukocyte antigen (HLA) complex play a critical role, with recent associations described between a T cell surface receptor for the costimulatory signal B7 (provided by antigen presenting cells; CTLA-4), and interleukin-1 (IL-1) receptor antagonist polymorphisms and autoimmune thyroid disease. Birth weight and hormonal changes constitute important endogenous influences on susceptibility, while iodine intake, stress, infections and toxins are all environmental factors. Once initiated, events within the thyroid determine whether or not autoimmunity is maintained. Originally, HLA class II molecule expression by thyroid cells was thought to be a likely trigger in thyroid autoimmunity. However, thyroid cells cannot provide a necessary costimulatory signal, required in addition to class II molecule-mediated antigen presentation, making them incapable of initiating activation of autoreactive T cells. Moreover, class II-positive thyroid cells can induce peripheral tolerance in T cells and so class II expression can be viewed as a protective mechanism. Later, in established disease, costimulatory signals are not required by T cells for further stimulation, and class II expression could then exacerbate disease.
authors.affiliation: Department of Medicine, University of Sheffield Clinical Sciences Centre, Northern General Hospital, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Weetman
mesh_terms: D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology*; D005260:Female; D006111:Graves Disease / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007037:Hypothyroidism / Q000276:immunology*; D008297:Male; D018448:Models, Immunological; D013961:Thyroid Gland / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II