Human NK cell repertoire diversity reflects immune experience and correlates with viral susceptibility

Abstract

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.

Identification of enhanced IFN-γ signaling in polyarticular juvenile idiopathic arthritis with mass cytometry

“…This is reminiscent of recent work using mass cytometry that demonstrated that synovial T cell infiltrates in rheumatoid arthritis were highly heterogeneous and that characterization of the CD4 T cell diversity facilitated potential discrimination of pathogenic and nonpathogenic variants of known T cell subsets (37,38). Similarly, NK cell heterogeneity identified with mass cytometry was shown to contribute to West Nile virus susceptibility (39,40).…”

Increased Proinflammatory Responses of Monocytes and Plasmacytoid Dendritic Cells to Influenza A Virus Infection During Pregnancy

“…Detailed staining protocols have been described elsewhere [11]. Staining panels are described in Supplementary Table 1.…”

Des cellules NK mémoire découvertes chez les primates

“…De nouveaux outils comme la cytométrie de masse, qui permettent de mesurer simultanément l'expression de plusieurs dizaines de récepteurs, ont récemment permis de montrer l'évolution du réper-toire des populations NK, lors des infections ou avec l'âge, et de mieux estimer sa complexité [12]. Ces nouvelles techniques apporteront peut-être des explications quant aux bases de la spécificité NK.…”