Graves' disease is associated with an altered CXCR3 and CCR5 expression in thyroid-derived compared to peripheral blood lymphocytes

The mechanisms by which T cells accumulate in the thyroid and support the autoimmune process in patients with Graves' disease (GD) are poorly understood. Chemokines and their receptors may be involved in this process. We have analysed the expression of CXCR3 and CCR5 as Th1-specific chemokine receptors, CCR3 as a marker for Th2 cells, CXCR4 (expressed on unprimed, naive T cells) and CCR2 (known to be involved in autoimmunity) on peripheral blood (PBL) and thyroid-derived lymphocytes (TL) using flow cytometry. Chemokine receptor expression on PBL of GD patients (n=16) did not differ from that of normal controls (n=10). In GD, CXCR3(+) (67.3+/-4.0% versus 45.7+/-2.1%) and CCR5(+) T cells (42.5+/-3.4% versus 18.8+/-2.1%) showed a significant enrichment in the TL compared to PBL. The positive cells were contributed mainly by the CD4(+) CD45R0(+) subset. TL are mostly primed CD45R0(+) T cells, but surprisingly, they had significantly higher levels of CXCR4(+) cells among TL (96.2+/-1.0%) compared to PBL (66.8+/-4.2%). However, CXCR4 has been induced during in vitro isolation of TL. There was no correlation between chemokine receptors and the level of TSH-receptor and thyroid peroxidase autoantibodies. CCR3(+) and CCR2(+) cells remained unchanged in TL compared to PBL. We could confirm the results using RT PCR and immunohistology. In summary, TL showed a different chemokine receptor pattern compared to PBL from the same patient. This indicates a role for CXCR3 and CCR5 in the recruitment of T cells to the thyroid in GD.