Specific phenotypic and functional features of natural killer cells from HIV-infected long-term non-progressors and HIV-controllers

Background: Recent evidence suggests that natural killer (NK) cells play a crucial role in the HIV pathogenesis. Long-term non-progressor (LTNP) and HIV-controllers are rare HIV-infected patients who control viral replication and show delayed disease progression. They represent fascinating models of natural protection against disease progression, and for studying the immunological response to the virus.
Methods: We have conducted an extensive analysis of the phenotypic and functional properties of CD56dim, CD56bright and CD56-/CD16+ NK cell subsets from LTNP and HIV-controllers, and compared them to HIV-progressors and healthy donors.
Results: Hierarchical clustering analysis of NK phenotypic markers revealed that LTNP and HIV-controllers, exhibit peculiar phenotypic features, associated with high levels of interferon-gamma, activation markers, and cytolytic activity in CD3-CD56+ NK cells against K562 target cells. More importantly, cytolytic activity against autologous CD4+ T cells is abrogated after treatment with anti-NKp44L mAb in LTNP and HIV-progressors, suggesting a key role of NKp44L. In contrast, in HIV-controllers and healthy donors, NKp44L expression on CD4+ T cells and autologous NK lysis were both poorly detected.
Conclusions: These results show that NK cells from LTNP and HIV-controllers display phenotypic and functional features, which suggests a consistent continuous involvement of the innate immune response in the control of AIDS pathogenesis.

V. Vieillard1, H. Fausther-Bovendo1, A. Samri2, P. Debré1, French Asymptomatic à Long Terme (ALT) ANRS-CO15
1INSERM UMR-S 945, Paris, France, 2IFR113, Paris, France