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Volume 6 Supplement 3

AIDS Vaccine 2009

P04-36. HIV-1-speficic antibody dependant cellular cytotoxicity (ADCC) médiated by primary NK cells

Background

Natural killer (NK) cells play an important role in antiviral immune responses; they kill HIV-1-infected cells either by direct lysis or through an antibody-dependent cellular cytotoxicity (ADCC) mechanism. HIV-1-specific ADCC were mainly detected using the CEM-NK target cell line. The aim of our study was to analyze the ADCC activity of various HIV-1-specific antibodies with an assay involving primary activated NK cells and autologous infected CD4 T-lymphocytes.

Methods

NK cells were purified from PBMC by magnetic bead selection. Autologous lymphocytes were stimulated by PHA for 3 days before being infected with different R5 HIV-1 strains for 3 additional days. NK cells previously activated with IL-2 or IL-15 were added to infected lymphocytes for 4 hours in the presence of different concentrations of anti-HIV-1-specific antibodies. The percentages of HIV-1-infected CD4 T-lymphocytes were measured by the detection of intracellular viral p24 antigen using flow cytometry. The immuno-phenotype of NK cells and the expression of CD107a (marker of NK cell degranulation) were determined in parallel.

Results

Our results show that in the absence of anti-HIV-1-specific antibodies, activated NK cells reduce by up to 50% the number of infected CD4 T-lymphocytes by direct lysis. In the presence of antibodies, the percentage of HIV-1-infected CD4 T-lymphocytes was further reduced and the percentage of NK cell degranulation was increased indicating HIV-1-specific ADCC activity. This activity was compared to other antibody inhibitory activities i.e. HIV-1 neutralization and Fcgamma receptors-mediated HIV-1 inhibition. Moreover, a correlation between the HIV-1-specific ADCC and the immuno-phenotype of NK cells was analyzed.

Conclusion

These results demonstrate that HIV-1-specific antibodies can inhibit HIV-1 replication in vitro by different mechanisms, including ADCC. If ADCC participates in HIV-1 protection, antibodies displaying ADCC should be induced by vaccination together with a stimulation of an innate NK immune response.

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Correspondence to M Delaporte.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Delaporte, M., Holl, V., Decoville, T. et al. P04-36. HIV-1-speficic antibody dependant cellular cytotoxicity (ADCC) médiated by primary NK cells. Retrovirology 6, P64 (2009). https://doi.org/10.1186/1742-4690-6-S3-P64

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Keywords

  • Natural Killer Cell
  • Activate Natural Killer Cell
  • Antibody Dependant Cellular Cytotoxicity
  • Antiviral Immune Response
  • Target Cell Line