Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 7, Issue 297, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aac5722
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Funding
- National Science Foundation [DGE-114740]
- Ruth L. Kirschstein National Research Service Award [1F31AI118469-01]
- NIH [U19AI089992, DP2AI11219301, P01 HSD 064915]
- Beckman Young Investigator Award
- California HIV Research Program IDEA award
- University of Washington Center for AIDS Research [P30 AI27757]
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Innate natural killer (NK) cells are diverse at the single-cell level because of variegated expressions of activating and inhibitory receptors, yet the developmental roots and functional consequences of this diversity remain unknown. Because NK cells are critical for antiviral and antitumor responses, a better understanding of their diversity could lead to an improved ability to harness them therapeutically. We found that NK diversity is lower at birth than in adults. During an antiviral response to either HIV-1 or West Nile virus, NK diversity increases, resulting in terminal differentiation and cytokine production at the cost of cell division and degranulation. In African women matched for HIV-1 exposure risk, high NK diversity is associated with increased risk of HIV-1 acquisition. Existing diversity may therefore decrease the flexibility of the antiviral response. Collectively, the data reveal that human NK diversity is a previously undefined metric of immune history and function that may be clinically useful in forecasting the outcomes of infection and malignancy.
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