Successfully treated HIV-infected patients have differential expression of NK cell receptors (NKp46 and NKp30) according to AIDS status at presentation

Immunol Lett. 2013 Apr;152(1):16-24. doi: 10.1016/j.imlet.2013.03.003. Epub 2013 Mar 26.

Abstract

Differences in innate immune responses may be associated with different capabilities of controlling HIV infection, not necessarily reflected by CD4(+) T-cell counts alone. We investigated by cytofluorometry the expression of NK cell receptors and ligands in 19 treated HIV-infected patients with CD4(+)<220 ml(-1) at presentation (11 AIDS, 8 non-AIDS) and 10 healthy donors. Expression of NKp46 and NKp30 was significantly higher in non-AIDS vs. AIDS patients. Overall, the level of NKp46 expression directly correlated with the degree of NK cell cytotoxicity. As compared to healthy donors, in both groups, there was a similar increase of CD69 and HLA-DR expression in NK cells that directly correlated with the presence of activation markers (HLA-DR) on CD4(+) and CD8(+) T cells. As compared to AIDS, in non-AIDS patients in vitro activated CD4(+) showed higher expression of MIC-A (NKG2D ligand), with significantly higher Nectin-2/DNAM-1 and MIC-A/NKG2D ratios. Thus, NK cell responses in AIDS and non-AIDS patients with similar CD4(+) counts significantly differ despite similar treatment. This suggests an involvement of innate mechanisms, in preventing AIDS-defining opportunistic infections in HIV infection and further suggests, that CD4(+) absolute counts alone, may be inadequate to explain differences in the clinical outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / immunology*
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Antiretroviral Therapy, Highly Active
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • HIV / immunology*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunity, Innate
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • NK Cell Lectin-Like Receptor Subfamily K / genetics
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Natural Cytotoxicity Triggering Receptor 1 / genetics
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism*
  • Natural Cytotoxicity Triggering Receptor 3 / genetics
  • Natural Cytotoxicity Triggering Receptor 3 / metabolism*
  • Nectins
  • Treatment Outcome

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • Cell Adhesion Molecules
  • Histocompatibility Antigens Class I
  • KLRK1 protein, human
  • MHC class I-related chain A
  • NCR1 protein, human
  • NCR3 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Natural Cytotoxicity Triggering Receptor 1
  • Natural Cytotoxicity Triggering Receptor 3
  • Nectins