Aberrantly Decreased Levels of NKG2D Expression in Children with Kawasaki Disease

Abstract

This study is designed to investigate the changes of NKG2D expression on CD8(+) T cells and CD3(-) CD56(+) NK cells in Kawasaki disease (KD). NKG2D/NKG2A expression on CD3(-) CD56(+) NK cells and CD8(+) T lymphocytes, and NKG2D ligands such as major histocompatibility complex I chain-related molecules A(MICA) and UL-16-binding proteins (ULBP-1) expression on CD14(+) mononuclear cells (MC) were analysed by flow cytometry in patients with KD. Real-time polymerase chain reaction (PCR) was used to evaluate the mRNA levels of interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α in CD14(+) cells. Plasma cytokine [IL-7, IL-12, IL-15, interferon (IFN)-γ and transforming growth factor (TGF)-β] concentrations were measured by ELISA. The levels of NKG2D on NK cells and CD8(+) T cells expression in acute phase of KD were significantly lower than those in normal controls (P<0.05), and the levels of NKG2D expression in the patients with coronary artery lesion (KD-CAL(+) ) were lower than those in patients with KD-CAL(-) . There was an upregulated tendency after treatment with IVIG. We found higher expression levels of proinflammatory cytokines from MC, such as IL-1β, IL-6 and TNF-α in patients with KD compared with the healthy controls (P<0.05). The concentrations of IL-7 and IL-15 were significantly decreased in acute phase of KD (P<0.05) and to some extent elevated after therapy with IVIG (P<0.05), while antagonistic cytokines like IFN-γ were increased in acute phase of KD (P<0.05) and reduced after therapy with IVIG (P<0.05). These results suggest that aberrantly decreased levels of NKG2D expression on NK cells and CD8(+) T cells might be one of the factors led to disturbed immunological function in patients with KD. Cytokines milieu could be important factors causing reduced expression of NKG2D.