Specific Phenotypic and Functional Features of Natural Killer Cells From HIV-Infected Long-Term Nonprogressors and HIV Controllers

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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 CD56dim, CD56bright 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.

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