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

Abstract

+ cells were mostly cd T cells, while ab 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+ cd T cells in TAO. Successful treatment apparently downregulates orbital monocyte recruitment and effects functional T cell knockout.

Orbit-Infiltrating Mast Cells, Monocytes, and Macrophages Produce PDGF Isoforms that Orchestrate Orbital Fibroblast Activation in Graves' Ophthalmopathy

“…In orbital tissue, PDGF-A and PDGF-B immunoreactivity was detected in monocytes, macrophages, and mast cells, which are well-known producers of PDGF (18,20,22). Monocyte infiltration into orbital tissue and their subsequent maturation into macrophages have been reported previously as important events in early and advanced GO (23)(24)(25)(26). In early GO, activated orbital fibroblasts secrete cytokines such as IL-6 and the glycosaminoglycan hyaluronan, which lead to inflammation and edema, respectively.…”

Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression

“…Decompression was carried out about 9 months after RTX therapy, when the patient's CAS was 2-3 and ophthalmopathy was burning out. The orbital tissue specimens were mainly constituted by fat and connective tissue and recently these components have been shown to be infiltrated by T-cells and to be actively involved in the autoimmune reactions (11). Lymphoid infiltration is usually observed in the orbit in disease of long duration (12) and since we cannot explain why both B and T-cells were not found in the orbit at both cytofluorimetry and immunohistochemistry, we can only interpret, but not prove, that orbital B-cell depletion was the consequence of RTX treatment.…”

“…TSH receptor hyperstimulation in the orbit leads to glycosaminoglycan secretion by pre-adipocytic fibroblasts and subsequent increase of the volume of intraorbital tissues (7,8). It has also been observed that eye muscles (9,10) and connective tissue and fat (11) are characteristically infiltrated by lymphocytes and are target of acute inflammatory reactions which eventually progress to scarring and stabilization of the eye disease (12). Recently, elevated TRAb have been correlated to the clinically active phase of TAO at onset (13) and to response to immunosuppressive therapy (14), although this does not prove a pathogenic role.…”

Graves' orbitopathy in a patient with adrenoleukodystrophy after bone marrow transplantation

“…It has been shown that orbital tissue from patients with GO is infiltrated with B and T cells, and it has been reported that orbital fibroblasts from Graves' patients can stimulate proliferation of autologous T cells (20) and that autologous T cells from patients with GO can stimulate proliferation of orbital fibroblasts, thus providing a mechanism by which infiltration of orbital tissue by autoimmune lymphocytes can drive the pathogenic features of GO (21). Another evidence of the involvement of T lymphocytes in the pathogenesis of GO derives from the observation that newborns from mothers with GO can be hyperthyroid as a result of possible passage of thyroid-stimulating IgG through the Figure 1 The patient affected by adrenoleukodystrophy, aged 12 years, at his baseline ophthalmic examination 6 years after bone marrow transplantation.…”