Correlation between thyroidal and peripheral blood total T cells, CD8⁺ T cells, and CD8⁺ T- regulatory cells and T-cell reactivity to calsequestrin and collagen XIII in patients with Graves’ ophthalmopathy

ABSTRACT

Purpose/aim of the study: Graves’ ophthalmopathy (GO) is closely related to the thyroid autoimmune disorder Graves’ disease. Previous studies have suggested roles for thyroidal CD8⁺ T cells and autoimmunity against calsequestrin-1 (CASQ)-1 in the link between thyroidal and orbital autoimmune reactions in GO. A role for autoimmunity against CollXIII has also been suggested. In this study, we aimed to investigate correlations between some thyroidal and peripheral blood T-cell subsets and thyroidal T-cell reactivity against CASQ1 and CollXIII in patients with GO.

Materials and methods: Fresh thyroid tissues were processed by enzyme digestion and density gradient to isolate mononuclear cells (MNCs). Peripheral blood MNCs were also isolated using density gradient. Flow-cytometric analysis was used to identify the various T-cell subsets. T -cell reactivity to CASQ1 and CollXIII was measured by a 5-day culture of the MNCs and BrdU uptake method.

Results: We found a positive correlation between thyroidal CD8⁺  T cells and CD8⁺ T-regulatory (T-reg) cells in patients with GO. Thyroidal T cells from two out of the three patients with GO tested (66.7%) showed a positive response to CASQ1, while thyroidal T cells from none of the six Graves’ Disease patients without ophthalmopathy (GD) tested showed a positive response to this antigen. Thyroidal T cells from these patient groups however, showed no significant differences in their response to CollXIII.

Conclusions: Our observations provide further evidence for a possible role of thyroidal CD8⁺ T cells, CD8⁺ T-reg cells and the autoantigen CASQ1 in the link between thyroidal and orbital autoimmune reactions of GO.

KEYWORDS:

• CD8⁺ T cells
• CD8⁺ T-regulatory cells
• Graves’ ophthalmopathy
• thyroid autoimmunity

Acknowledgments

We would like to acknowledge Nepean Medical Research Foundation and Nepean Blue Mountains Local Health District for their funding to support this work. We also would like to thank Professor Leigh Delbridge for his help in patient recruitment and Associate Professor Stephen Fuller for his support of the project.

Conflict of interest statement

The authors declare no conflict of interest regarding the publication of this paper.