Activation of NK Cells by ADCC Antibodies and HIV Disease Progression

J Acquir Immune Defic Syndr. 2011 Oct 1;58(2):127-31. doi: 10.1097/QAI.0b013e31822c62b9.

Abstract

Antibody-dependent cellular cytotoxicity (ADCC) is of considerable interest as an immune response that may facilitate the control of HIV infection. We studied ADCC responses prospectively in a cohort of 79 HIV-positive subjects followed up for a mean of 2.3 years without antiretroviral therapy. We used a novel assay of the ability of ADCC to activate natural killer (NK) cells, either from the same HIV-positive subject or from a healthy blood donor. We found that ADCC responses to either gp140 Env protein or HIV peptide pools were common in HIV-positive subjects when NK cells from the HIV-positive subject were used but did not correlate with markers of HIV disease progression. In contrast, ADCC responses to whole gp140 Env protein were strongly associated with a slower decline in CD4 T-cell loss when healthy donor NK cells were used as effectors. Our data had implications for induction of the most effective ADCC responses by HIV vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibody-Dependent Cell Cytotoxicity / immunology*
  • CD4 Lymphocyte Count
  • Disease Progression*
  • Female
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Human Immunodeficiency Virus Proteins / blood
  • Human Immunodeficiency Virus Proteins / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Longitudinal Studies
  • Lymphocyte Activation
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Male
  • Middle Aged
  • Prospective Studies
  • Viral Load / immunology
  • Young Adult
  • env Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • Human Immunodeficiency Virus Proteins
  • Lysosomal-Associated Membrane Protein 1
  • env Gene Products, Human Immunodeficiency Virus
  • gp140 envelope protein, Human immunodeficiency virus 1
  • Interferon-gamma