title: The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases.
abstract: 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.
authors.affiliation: Institute of Anatomy, University of Leipzig, Leipzig, Germany. ausg@medizin.uni-leipzig.de
authors.forename: G
authors.initials: G
authors.lastname: Aust
authors.forename: D
authors.initials: D
authors.lastname: Sittig
authors.forename: L
authors.initials: L
authors.lastname: Becherer
authors.forename: U
authors.initials: U
authors.lastname: Anderegg
authors.forename: A
authors.initials: A
authors.lastname: Schütz
authors.forename: P
authors.initials: P
authors.lastname: Lamesch
authors.forename: E
authors.initials: E
authors.lastname: Schmücking
mesh_terms: D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000378:metabolism*; D002828:Choristoma / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006111:Graves Disease / Q000276:immunology / Q000378:metabolism; D006801:Humans; D017254:Leukemic Infiltration / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue; D008297:Male; D008875:Middle Aged; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism*; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine