The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases

Objective: Graves' disease (GD) and Hashimoto's thyroiditis (HT) are characterized by lymphocytic infiltrates partly resembling secondary lymphoid follicles in the thyroid. CXCR5 and its ligand CXCL13 regulate compartmentalization of B- and T-cells in secondary lymphoid organs. The aim of the study was to elucidate the role of this chemokine receptor-ligand pair in thyroid autoimmunity. Methods: Peripheral blood and thyroid-derived lymphocyte subpopulations were examined by flow cytometry for CXCR5. CXCR5 and CXCL13 cDNA were quantified in thyroid tissues by real-time RT-PCR. Results: We found no differences between the percentages of peripheral blood CXCR5(+) T- and B-cells in GD patients (n = 10) and healthy controls (n = 10). In GD patients, the number of memory CD4(+) cells expressing CXCR5 which are functionally characterized as follicular B helper T-cells is higher in thyroid-derived (18 +/- 3%) compared with peripheral blood T-lymphocytes (8 +/- 2%). The highest CXCL13 mRNA levels were found in HT (n = 2, 86.1 +/- 1.2 zmol (10(-21) mol) cDNA/PCR) followed by GD tissues (n = 16, 9.6 +/- 3.5). Only low amounts were determined in thyroid autonomy (TA) (n = 11) thyroid tissues, irrespective of whether the autonomous nodule (0.5 +/- 0.1) or the surrounding normal tissue (1.8 +/- 0.7) had been analyzed. The same differences were found for CXCR5 (HT: 179.1 +/- 6.8; GD: 17.4 +/- 10.6; TA(nodule): 0.8 +/- 0.5; TA(normal): 4.4 +/- 3.6). In GD, there is a correlation between CXCL13 and CXCR5 mRNA levels and the number of focal lymphocytic infiltrates and germinal centers as well as anti-thyroperoxidase but not anti-TSH receptor autoantibodies. Conclusions: CXCR5 and CXCL13 play an essential role in maintaining B- and T-cells in lymphocytic infiltrates and ectopic follicles in thyroid tissue from patients affected by autoimmunity.