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