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Thyroid associated ophthalmopathy: evidence for CD4+ γδ T cells; de novo differentiation of RFD7+ macrophages, but not of RFD1+ dendritic cells; and loss of γδ and αβ T cell receptor expression

Abstract

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; αβ and γδ 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 γδ T cells, while αβ 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+ γδ T cells in TAO. Successful treatment apparently downregulates orbital monocyte recruitment and effects functional T cell knockout.

  • TAO
  • CD4
  • CD33
  • γδ T lymphocytes
  • Graves’ ophthalmopathy
  • DC, dendritic cell
  • TAO, thyroid associated ophthalmopathy
  • TCR, T cell receptor
  • Th, T helper
  • TAO
  • CD4
  • CD33
  • γδ T lymphocytes
  • Graves’ ophthalmopathy
  • DC, dendritic cell
  • TAO, thyroid associated ophthalmopathy
  • TCR, T cell receptor
  • Th, T helper

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