Inhibition of the NKG2D-signaling pathway ameliorates the disease course of experimental autoimmune encephalomyelitis (EAE).

<p>(<b>A</b>) EAE disease course was reduced in NKG2D-blocking-antibody-treated C57BL/6 mice (black arrows, days of injection, clone CX5) compared with mice treated with an isotype control (two independent experiments, <i>n</i> = 8 each). Myelin oligodendrocyte protein (MOG) recall assays and flow cytometry were performed at disease onset (gray arrow). (<b>B</b>) ELISAs for IFN-γ production and the splenocyte stimulation index indicative of cell proliferation showed no significant differences for splenocytes of antibody- and isotype-treated mice at disease onset (<i>n</i> = 5 mice per group). (<b>C</b>) Flow cytometric quantification of NKG2D⁺ CD4⁺ and CD8⁺ lymphocytes invading the brain at disease onset of EAE (<i>n</i> = 5 mice per group, clone 7 used for staining). (<b>D</b>) Representative immunohistochemical staining of spinal cord samples from isotype- or anti-NKG2D-treated mice (<i>n</i> = 10 per mouse; <i>n</i> = 5 mice per group) at the disease maximum of EAE and quantification of the area of infiltrating cells (hematoxylin and eosin [H&E] staining, highlighted area) and area of demyelination (luxol fast blue [LFB] staining, highlighted area). (<b>E</b>) In vivo blockade of NKG2D by soluble NKG2D (sNKG2D) delayed the onset of EAE when administered before disease onset (left panel). In contrast, the administration of sNKG2D after disease onset had no significant effects (right panel). (<i>n</i> = 6 mice per group). *P < 0.05. ns, not significant.