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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
  1. A K Eckstein1,
  2. B Quadbeck2,
  3. S Tews1,
  4. K Mann2,
  5. C Krüger3,
  6. C H Mohr3,
  7. K-P Steuhl1,
  8. J Esser1,
  9. R K Gieseler4
  1. 1Department of Ophthalmology, Essen University Hospital, Essen, Germany
  2. 2Department of Medicine, Division of Endocrinology, Essen University Hospital, Essen, Germany
  3. 3Department of Oral and Maxillofacial Surgery, Essen University Hospital, Essen, Germany
  4. 4Laboratories of Immunology, Molecular Biology, and Virology, LTBH Medical Research Institute, Beverly Hills, CA, USA and Department of Pharmaceutics, Health Science Center, University of Florida, Gainesville, FL, USA
  1. Correspondence to: Adj Professor R K Gieseler LTBH Medical Research Institute, Robertson Center, 200 N Robertson Blvd./Suite 208, Beverly Hills, CA 90211–1769, USA; RGieselerlettherebehope.org

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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