Natural killer (NK) cells and dendritic cells (DCs) are two distinct cell types of innate immunity. It is known that the in vitro interaction of human NK cells with autologous DCs results in DC lysis. Here we show that contact-dependent interactions between activated human NK cells and immature DCs (iDCs) provides a “control switch” for the immune system. At low NK/DC ratios, this interaction dramatically amplifies DC responses, whereas at high ratios it completely turns off their responses. Specifically, culture of activated human NK cells with iDCs, at low NK/DC ratios (1:5), led to exponential increases in DC cytokine production, which were completely dependent on cell-to-cell contact. DC maturation was also driven by cognate interactions with NK cells and maturation was dependent on endogenously produced TNF-α in the culture. At slightly higher NK/DC ratios (5:1), inhibition of DC functions was the dominant feature due to potent killing by the autologous NK cells. Resting NK cells also stimulated autologous DC maturation in a TNF-α/contact-dependent manner, however, increasing the NK/DC ratio only led to an enhancement of this effect.

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65–89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.