Nature killer cells in the central nervous system

Natural killer (NK) cells, a prominent component of the innate immune system, are large granular lymphocytes that respond rapidly to a variety of insults via cytokine secretion and cytolytic activity. Recently, there has been growing insight into the biological functions of NK cells, in particular into their roles in infection, tumorurveillance and autoimmunity. Under these pathophysiological circumstances, NK cells readily home to the central nervous system (CNS) tissues to combat infection and presumably to curb progression of tumor. Bystander neuronal and/or glial cell damage can occur in this setting. Paradoxically, NK cells appear to have an inhibitory role for autoimmune responses within the CNS. As in the periphery, NK cells act in concert with T cells and other lymphocytes responsible for CNS pathology and immune regulation. Insights into the molecular signals and pathways governing the diverse biological effects of NK cells are keys for designing NK cell-based therapy for CNS infections, tumor and autoimmune diseases.NK cells readily accumulate in homing to CNS tissues under the pathophysiological situations. This process is tightly controlled by a number of chemokines and chemokine receptors. There is ample of evidence that NK cells within the CNS contribute to the control of infections and might limit progression of certain tumor. Bystander neuronal and/or glial cell damage can occur. In certain autoimmune conditions of the CNS, NK cells appear to have an inhibitory role. Disassociation of disease-inhibiting versus disease-promoting effects of NK cells is a key to harnessing NK cells for therapeutic purposes. To achieve this goal, a generation of genetic models with selective NK cell deficiency, and development of reagents (antibodies) for visualizing subsets of NK cells in situ will be necessary.