INTRODUCTION
Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disorder with diverse clinical symptoms at onset and throughout the disease. There are at least three major onset types of JIA: pauciarticular, polyarticular, and systemic. CD4+ T cells are important in the initiation and propagation of JIA, leading to recruitment of innate and adaptive immune cells and the production of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-17, and interferon-gamma (IFN γ), which collectively lead to chronic inflammation [1]. The activation of CD4+ T cells depends on the interaction with antigen present cells. Activation requires T cell receptor and a costimulatory signal.
Natural-killer group 2 member D (NKG2D) is a widely-active receptor detectable on NK cells and several subsets of T cells, including CD8+ T cells, γδ T cells, and NKT cells in steady state, and CD4+ T cells under certain pathological conditions, such as infection, cancer, and autoimmune disease (AID) [2]. An NKG2D-dependent regulatory role in NK cells was reported in the inflammation of systemic JIA [3]. Additionally, NKG2D provides a costimulatory signal for activation of CD4+ T cells. CD4+NKG2D+ T cells are recognized as a novel subset of T lymphocytes in many AIDs, such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Crohn disease and type 2 diabetes. These cells interact with NKG2D ligand (NKG2DL)-positive cells, such as synoviocytes, endothelial cells, and epithelial cells, causing autoreactive T cell stimulation and AID [4-8]. However, the immune functions and clear mechanism of CD4+NKG2D+ T cells in AID are still controversial and unclear [9,10].
There is a lack of research regarding CD4+NKG2D+ T cells in JIA. We addressed this by investigating the activity of CD4+NKG2D+ T cells in different clinical subtypes of JIA patients. As well, we assessed the influence of NKG2D receptor on the differentiation of CD4+ T cell subgroups during interaction with the strongest antigen presenting cell type, dendritic cells (DCs).
METHODS