Dendritic cells in autoimmune thyroid disease

Abstract

Abstract. Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20–30% were seen in contact with now-present intrathyroidal T-helper lymphocytes. The so-formed lymphoid cell aggregates were predominantly small (< 10 cells), but very large aggregates could also be detected. These large accumulations were highly organized and composed of T-cell zones, B-cell zones and numerous plasma cells. Such accumulations are reminiscent of secondary lymphoid organs. In view of these morphological data it is conceivable that thyroid dendritic cells are of prime importance in the presentation of autoantigen in thyroid autoimmune disease. Throughout the process of autosensitization in the BB/W rat thyroid epithelial cells stayed negative for Class II MHC determinants. This shows that Class II expression on thyrocytes is not prerequisite for thyroid autoimmunity to develop.