Catherine A. Blish
Novel strategies to develop comprehensive understanding of antiviral NK cell function
Stanford University School of Medicine
Medicine, Division of Infectious Diseases and Geographic Medicine
The combinatorial diversity of natural killer (NK) cells is critical to rapid antiviral responses, but the origins of that diversity are unclear. Here we show that human NK diversity is distinct from adaptive immune diversity in that it accumulates with antigen experience and alters function. NK diversity is low at birth and reaches a stable level in the absence of perturbation in healthy adults, but remains exquisitely sensitive to perturbation. In a cohort of African women, a higher level of NK cell diversity is associated with increased risk of HIV-1 acquisition. Exposure to both HIV-1 and West Nile virus-infected cells in vitro increases NK cell diversity, resulting in terminal differentiation and cytokine production at the cost of cell division and cytotoxicity. Collectively, the data reveal that human NK cell diversity is a previously undefined metric of immune history and function that may predict viral susceptibiliy.