title: CXCR6 within T-helper (Th) and T-cytotoxic (Tc) type 1 lymphocytes in Graves' disease (GD).
abstract: OBJECTIVE
  In Graves' disease (GD), stimulating anti-TSH receptor antibodies are responsible for hyperthyroidism. T-helper 2 (Th2) cells were expected to be involved in the underlying immune mechanism, although this is still controversial. The aim of this study was to examine the expression of CXCR6, a chemokine receptor that marks functionally specialized T-cells within the Th1 and T-cytotoxic 1 (Tc1) cell pool, to gain new insights into the running immune processes.
  
  
  METHODS
  CXCR6 expression was examined on peripheral blood lymphocytes (PBLs) and thyroid-derived lymphocytes (TLs) of GD patients in flow cytometry. CXCR6 cDNA was quantified in thyroid tissues affected by GD (n = 16), Hashimoto's thyroiditis (HT; n = 2) and thyroid autonomy (TA; n = 11) using real-time reverse transcriptase PCR.
  
  
  RESULTS
  The percentages of peripheral CXCR6(+) PBLs did not differ between GD and normal subjects. CXCR6 was expressed by small subsets of circulating T-cells and natural killer (NK) cells. CXCR6(+) cells were enriched in thyroid-derived T-cells compared with peripheral CD4(+) and CD8(+) T-cells in GD. The increase was evident within the Th1 (CD4(+) interferon-gamma(+) (IFN-gamma(+))) and Tc1 (CD8(+)IFN-gamma(+)) subpopulation and CD8(+) granzyme A(+) T-cells (cytotoxic effector type). Thyroid-derived fibro-blasts and thyrocytes were CXCR6(-). There was no significant difference between the CXCR6 mRNA levels in GD compared with HT and normal TA tissues. The lowest CXCR6 mRNA levels were obtained from thyroid nodules from TA patients and GD patients with low thyroid peroxidase autoantibody levels.
  
  
  CONCLUSIONS
  CXCR6 was overexpressed in Th1 and Tc1 TLs compared with PBLs in GD. CXCR6 could be a marker for lymphocytes that have migrated into the thyroid and assist in the thyroid, independently of the bias of the underlying disease.
authors.affiliation: Institute of Anatomy, University of Leipzig, Germany. ausg@medizin.uni-leipzig.de
authors.forename: G
authors.initials: G
authors.lastname: Aust
authors.forename: M
authors.initials: M
authors.lastname: Kamprad
authors.forename: P
authors.initials: P
authors.lastname: Lamesch
authors.forename: E
authors.initials: E
authors.lastname: Schmücking
mesh_terms: D000293:Adolescent; D000328:Adult; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000032:analysis* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000032:analysis* / Q000235:genetics; D011991:Receptors, Virus / Q000032:analysis* / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry*; D018417:Th1 Cells / Q000737:chemistry*; D013961:Thyroid Gland / Q000737:chemistry
chemical_list: C106330:CXCR6 protein, human; D018076:DNA, Complementary; D012333:RNA, Messenger; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus