ABSTRACT
Objectives: To explore roles of NKG2D in interactions of
CD4+ T cells and dendritic cells (DCs) in juvenile
idiopathic arthritis (JIA) patients
Methods: Peripheral blood from active JIA patients and healthy
controls were used for flow cytometry assessments of
NKG2D+CD4+ T cells and expressions
of MICA and MICB on DCs. NKG2D genetically modified
CD4+ T cells resulted from transfection with
lentiviral vectors harboring NKG2D and NKG2D siRNA. ELISA measured
supernatant cytokines in co-cultured CD4+ T cells and
DCs. CD4+ T cell subgroups, MICA and MICB expression
on DCs was determined by flow cytometry and transcription factors by
real-time PCR.
Results: All JIA patients had significantly higher content of
CD4+NKG2D+ T cells compared to
healthy controls (P < 0.01). Expression of NKG2D on
CD4+ T cells, and MICA and MICB on DCs were
significantly greater in articular JIA than systemic JIA (P <
0.05). NKG2D induced IL-12 and suppressed IL-10 and TGF-β from
CD4+ T cells, increased IFN-γ+ CD4+
T and IL-17+ CD4+ T cells, RORc and
T-bet, but reduced CD25+ Foxp3+CD4+ T cells, IL-4+CD4+ T cells, Foxp3, and GATA3 in JIA patients
(P<0.05). NKG2D increased IL-12 and T-bet by
CD4+ T cells in healthy controls (P<0.05).
NKG2D decreased IL-10 and increased CD83, MICA, and MICB of DCs via
interaction with CD4+ T cells in JIA and control
patients (P<0.05).
Conclusions: NKG2D regulates differentiation of
CD4+ T cells directly and the maturation of DCs
indirectly. Targeting NKG2D may be a potential therapy for JIA.
Key words: NKG2D, juvenile
idiopathic arthritis, CD4+ T cell, differentiation,
dendritic cell