Patients With Autoimmune Thyroiditis Show Diminished Levels and Defective Suppressive Function of Tr1 Regulatory Lymphocytes

J Clin Endocrinol Metab. 2018 Sep 1;103(9):3359-3367. doi: 10.1210/jc.2018-00498.

Abstract

Context: T regulatory type 1 (Tr1) cells are a subpopulation of T lymphocytes (CD4+CD49+LAG-3+IL-10+) that exert a considerable immunosuppressive effect. However, their possible role in autoimmune thyroid disease (AITD) has not been explored so far.

Purpose: To analyze the levels and function of Tr1 cells in peripheral blood and thyroid tissue of patients with AITD.

Design: Cases and controls, observational study.

Setting: Department of Endocrinology, Hospital Universitario de la Princesa, Madrid, Spain.

Patients: Thirty-eight patients with AITD (23 with Graves disease and 15 with Hashimoto thyroiditis) and 26 controls.

Intervention: Multiparametric flow cytometry and immunofluorescence techniques were used to analyze the levels in peripheral blood (n = 38) and thyroid mononuclear cells (n = 5). An in vitro assay of suppression of cellular activation and cytokine release was performed to study the function of Tr1 cells.

Main outcome measure: Levels and function of Tr1 cells in patients with AITD and controls.

Results: Levels of Tr1 cells were significantly diminished in peripheral blood from patients with AITD. Functional studies showed that Tr1 cells from patients with AITD exhibit a diminished suppressive function compared with healthy controls. Tr1 levels were associated with disease severity, including longer duration of the disease and ophthalmopathy activity, and with autoantibody titers.

Conclusions: The low levels of Tr1 cells and their diminished function may have a relevant role in the defective immune-regulatory function characteristic of patients with AITD.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Graves Disease / blood*
  • Graves Disease / immunology
  • Hashimoto Disease / blood*
  • Hashimoto Disease / immunology
  • Humans
  • Lymphocyte Activation / immunology*
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology*
  • Thyroid Gland / immunology
  • Thyroiditis, Autoimmune / blood*
  • Thyroiditis, Autoimmune / immunology