Specific phenotypic and functional features of natural killer cells from HIV-infected long-term nonprogressors and HIV controllers.
BACKGROUND
Recent evidence suggests that natural killer (NK) cells play a crucial role in the HIV pathogenesis. Long-term nonprogressor (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 CD56, CD56 and CD56/CD16 NK cell subsets from LTNP and HIV-controllers, and compared them with 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-g, activation markers, and cytolytic activity in CD3CD56 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 and suggest a consistent continuous involvement of the innate immune response in the failure to control viral replication. Collectively, these data may have important implication in the design of new anti-HIV therapeutical strategies based on the particular functional activity of NK cells.
Vieillard
Vincent
V
INSERM UMR-S 945, Laboratoire Immunité et Infection, Hôpital Pitié-Salpêtrière, Paris, France. vincent.vieillard@upmc.
Fausther-Bovendo
Hugues
H
Samri
Assia
A
Debré
Patrice
P
D017252:CD3 Complex / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D016000:Cluster Analysis; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016130:Immunophenotyping; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000276:immunology
D017252:CD3 Complex; D019002:CD56 Antigen; C112837:NCR2 protein, human; D055629:Natural Cytotoxicity Triggering Receptor 2