NKG2D indirectly regulates activation of DCs by interaction with
CD4+ T cells
The regulation of NKG2D on DCs was investigated by co-culturing DCs from
JIA patients and healthy controls with irradiated CD4+T cells with the genetic modifications of NKG2D. The cytokines secreted
by DCs are shown in Figure 5A. In healthy controls, NKG2D significantly
decreased the secretion of IL-10 and TGF-β by DCs via the
interaction with CD4+ T cells (P<0.05). No
significant effect on the production of IL-12 was evident
(P>0.05). Additionally, NKG2D decreased the secretion of
IL-10 by DCs of JIA patients via the interaction with
CD4+T cells (P<0.05). Production of TGF-β
and IL-12 was not influenced (P>0.05).
The expressions of the costimulatory molecules CD80 and CD86, and DC
maturation markers CD83 and the MHC II receptor HLA-DR were analyzed
(Figure 5B). CD83 expression on DCs of JIA patients and healthy controls
rose significantly upon interaction with NKG2D overexpressing
CD4+ T cells (P<0.05) and vice versa. This
expression was significantly lowered by interaction with NKG2D silenced
CD4+ T cells (P<0.05). NKG2D genetic
modifications had no statistical influences on cellular markers of CD80,
CD86 and HLA-DR in the JIA or healthy control groups
(P>0.05).
The expressions of the NKG2D ligands MICA and MICB on DCs were tested by
flow cytometry (Figure 5C and 5D). NKG2D indirectly upregulated the
expression of MICA and MICB on DCs in JIA patients and healthy controls
by LV-NKG2D modification in CD4+ T cells
(P<0.05). NKG2D also significantly decreased MICA and MICB
expressions by LV-siRNA modified CD4+ T cells
(P<0.05).