Thyroid associated ophthalmopathy: evidence for CD4(+) gammadelta T cells; de novo differentiation of RFD7(+) macrophages, but not of RFD1(+) dendritic cells; and loss of gammadelta and alphabeta T cell receptor expression.

AIM: To characterise periorbital immune cells (stages, kinetics) in active and inactive thyroid associated ophthalmopathy (A-TAO; I-TAO). METHODS: In orbital tissue cryosections of patients with A-TAO (n = 15), I-TAO (n = 11), and healthy controls (n = 14), adipose and fibrovascular areas were evaluated for MHC II(+) cells, CD45(+) total leukocytes, myeloid cells (CD33(+) monocytes; CD14(+) macrophages; mature RFD7(+) macrophages; RFD1(+) dendritic cells (DCs)), and lymphoid cells (CD4(+) T cells; alphabeta and gammadelta T cells; CD20(+) B cells). Results are expressed as medians and 5% confidence intervals. RESULTS: In fibrovascular septae, a surge of CD33(+) immigrants clearly correlating with disease activity generated significantly increased (p<0.05) percentages of CD14(+) and RFD7(+) macrophages. Intriguingly, CD4(+) cells were mostly gammadelta T cells, while alphabeta T helper cells were much less frequent. Successful treatment rendering TAO inactive apparently downregulates monocyte influx, macrophage differentiation, and T cell receptor expression. Similar trends were recorded for adipose tissue. Interestingly, RFD1(+) DCs were completely absent from all conditions examined. CONCLUSION: A-TAO coincides with periorbital monocyte infiltration and de novo differentiation of macrophages, but not DCs. The authors discuss a novel potential role for inflammatory CD4(+) gammadelta T cells in TAO. Successful treatment apparently downregulates orbital monocyte recruitment and effects functional T cell knockout.

Maturation of thyroidal dendritic cells in Graves' disease.

Because thyroidal dendritic cells (t-DC) may be implicated in the pathogenesis of Graves' disease (GD), we compared t-DC in thyroid sections of patients with GD (n = 15) and control patients with toxic (TG; n = 12) or non-toxic goitre (NG; n = 12). Goitres in GD, but not TG or NG, were populated with three discernible t-DC phenotypes. (i) Immature t-DC (major histocompatibility complex (MHC) II+/CD40-/CD80-) were located perifollicularly (95% of the patients with GD, but only 55% of TG and 51% of NG patients); numbers of such t-DC were significantly elevated in GD (P < 0.001). (ii) Partially matured CD80+ t-DC were present in connective tissue (73% of the patients) and focal interstitial clusters (40% of the patients). In 53% of the patients with GD, single as well as clustered interstitial t-DC expressed CD40. (iii) However, phenotypically mature t-DC (MHC II+/CD40+/CD80+/RFD1+) were only present in clusters and colocalized with activated CD4+/MHC class II+ T-helper (Th) cells. Expression of CD54 and CD83 did not significantly differ among the groups. The phenotype of intrathyroidal DC in GD thus supports their role as potential (co)stimulators of thyroid autoimmunity.