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

Endocr Res. 2018 Nov;43(4):264-274. doi: 10.1080/07435800.2018.1470639. Epub 2018 May 22.

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.

MeSH terms

  • Adult
  • Calsequestrin / pharmacology*
  • Collagen Type XIII / pharmacology*
  • Female
  • Graves Disease / blood
  • Graves Disease / metabolism*
  • Graves Ophthalmopathy / blood
  • Graves Ophthalmopathy / metabolism*
  • Humans
  • Male
  • Middle Aged
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism

Substances

  • Calsequestrin
  • Collagen Type XIII