Quantitative and Functional Analysis of PD-1+ NK Cells in Patients with Autoimmune Thyroid Disease

Abstract

Context: Natural killer (NK) cells have an important role in innate immunity and in the regulation of immune response.The role of NK cells expressing the programmed cell death protein-1 (PD-1) regulatory receptor has not been explored in patients with autoimmune thyroid disease (AITD). Purpose: To analyze the levels and function of PD-1+ NK cells in samples from AITD patients. Design: Cases and controls, observational study. Setting: Hospital Universitario la Princesa, Spain. Patients: Forty patients with AITD, 16 with Hashimoto thyroiditis (HT), 24 with Graves’ disease (GD), and 15 healthy controls. Intervention: Multiparametric flow cytometry analysis of peripheral blood NK cells. In vitro assays of cytotoxic activity of NK cells, and synthesis of cytokines. Main outcome measures: Levels and function of PD-1+ NK cells in blood samples from AITD patients and controls. Results: Increased levels of NK cells and the CD56dimPD-1+ subset were observed in GD patients. In HT, an enhanced expression of the regulatory receptors NKG2A and NKG2C by CD56brightPD-1+ NK cells was detected. AITD patients showed an increased synthesis of IL-10 by CD56brightPD-1– NK cells, whereas CD56dimPD-1+ cells from GD patients exhibited an enhanced production of interferon-γ. PD-1+ NK cells from patients with GD and HT showed an increased cytotoxic activity. Significant associations were observed in patients with GD or HT between the levels of PD-1+ NK cells and clinical laboratory parameters. Conclusions: The different abnormalities in NK cell subset levels, in the expression of PD-1 and its function in AITD patients’ further support the complex role of these cells in this pathogenesis.