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High Endothelial Venules Present in Lymphoid Cell Accumulations in Thyroids Affected by Autoimmune Disease: A Study in Men and BB Rats of Functional Activity and Development^*

Laboratory for Clinical Immunology, Department of Pathology, Free University Hospital Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: P. J. Kabel, Laboratory for Clinical Immunology, Department of Pathology, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

High endothelial venules (HEVs) derive their name from the cuboidal high walled shape of the endothelial cells and are found in T-cell areas of a wide variety of lymphoid tissues. The function of HEVs is to attract lymphocytes to lymphoid tissues, and they are thus of importance in lymphocyte recirculation.

We investigated the immunohistochemical presence and localization of HEVs in thyroid tissue obtained at surgery from 13 patients with Graves’ disease and 3 patients with Hashimoto’s disease using the monoclonal antibody HECA 452, which reacts with an epitope on human HEVs. HEVs were found in large confined lymphocytic accumulations in 7 of the 13 Graves’ disease glands and all of the Hashimoto’s disease glands. These lymphocytic accumulations showed a high grade of architecture and were composed of a central B-cell follicle and a T-cell area in which the HEVs were present. The HEV-containing T-cell area formed a corona around the B-cell follicle. Plasma cells were found at the periphery of the intrathyroidally developed lymphoid tissue. In BB rats, an animal model for spontaneous autoimmune thyroid disease, the development of such HEVs containing intrathyroidal lymphoid tissue was a rather late phenomenon in the autoimmune process occurring after the appearance of anticolloid antibodies in the circulation and after initial immune acitivity of the thyroid draining lymph nodes. The actual development of the intrathyroidal lymphoid tissue was initiated by accumulation of lymphocytes around dendritic cells forming small cellular clusters. These small clusters later developed into larger formations in which HEVs were detectable.

The adherence of B- and T-lymphocytes to human intrathyroidal HEVs was additionally studied using an in vitro adherence assay. B-Lymphocytes preferentially adhered to thyroidal HEVs. This adherence pattern is similar to that of HEVs in mucosaassociated lymphoid tissue (tonsils and Peyer’s patches).

We conclude that lymphoid tissue with a lymphocyte recirculation pattern similar to that of mucosa-associated lymphoid tissue can be found in thyroid glands involved in a process of autoimmune reactivity; the BB rat study suggests that the development of such tissue occurs during the chronic phases of the process.

^* This work was supported by a grant from the Dutch Organization for the Advancement of Pure Research (NWO-MEDIGON 900-540-140).

Received July 1, 1988.

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