Do Human Natural Killer Cells Acquire Immune Memory to Viral Infections?
Natural killer (NK) cells have traditionally been considered members of the innate immune system. Recently, in a mouse model of cytomegalovirus, our lab has demonstrated that NK cells undergo clonal expansion during acute viral infection, the population contracts when virus is controlled, but remarkably infection induces a population of "memory" NK cells. These cells are long-lived, respond more robustly when re-challenged, and provide enhanced host protection against re-infection. We hypothesize that human NK cells that have been clonally expanded by pathogen exposure can be identified by the CD57 marker and that NK cell that have responded to human cytomegalovirus (HCMV) will preferentially express the activating NKG2C receptor. We propose experiments to define the functional properties and transcriptional signature of these human NK cell populations to obtain pre inary results to demonstrate feasibility for a major NIH grant on this subject. If "memory" NK cells do exist in humans, these may be important in the control of chronic infections such as HIV, HCMV, or hepatitis C, and provide new therapeutic opportunities for vaccination of NK cells against pathogens.