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

Abstract

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.