Behaviorally conditioned modulation of natural killer cell activity: enhancement of baseline and activated natural...

Natural killer (NK) cells comprise a sub-population of lymphocytes functionally defined by their ability to spontaneously lyse select tumor and virally infected cells. NK cell lytic function is sensitive to modulation by cytokines and neuroendocrine mediators. Behavioral conditioning trains an animal to cognitively associate a novel environmental cue (i.e. odor) with a physiologically active agent (i.e. Polylnosinic:PolyCytidilic acid, Poly I:C). Poly I:C induces interferon production resulting in activation of NK cells and enhanced NK cell lytic activity. Subsequent to behavioral conditioning, independent presentation of the odor should elicit similar responses (enhanced NK cell activity). We have shown that animals pre-exposed to the conditioning apparatus or manual restraint prior to behavioral conditioning demonstrate enhanced baseline NK cell activity or no effects respectively. To assess the influence of NK cell activation in conjunction with behavioral conditioning, we have re-presented the odor to animals with activated or baseline NK activity. Lymphocytes were then incubated for five days with IL-2 and cellular cytotoxic activity re-assessed. Behavioral conditioning significantly enhanced baseline and activated NK cell activity in animals previously exposed to the conditioning apparatus. No differences in lytic activity versus NK sensitive targets were observed following IL-2 activation. In contrast, animals manually restrained prior to conditioning showed no differences in baseline or in vivo activated NK activity, but previously non-activated lymphocytes stimulated with IL-2 demonstrated significantly higher lytic activity in conditioned animals re-presented with the odor. These results demonstrate central nervous system (CNS) modulation of NK cell activity and the presence of an interplay between cytokine activation and responsiveness to CNS immunoregulatory signals.