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