Detection of HIV-1-specific T-cell immune responses in highly HIV-exposed uninfected individuals by in-vitro dendritic cell co-culture

AIDS. 2015 Jul 17;29(11):1309-18. doi: 10.1097/QAD.0000000000000728.

Abstract

Background: Although virus-specific responses are rarely detected by conventional approaches, we report here the detection of T-cell responses in HIV-exposed seronegative (HESN) patients by two distinct assays.

Methods: HIV-specific T-cell responses were analyzed by enzyme-linked immunospot in peripheral blood mononuclear cells from HESN patients after a 48-h co-culture with boosted dendritic cells. Additionally, a boosted flow cytometry approach was used to capture antiviral T-cell responses. Host genetic factors and T-cell activation were also analyzed to assess their implication on HIV exposure.

Results: Of the 45 HESN individuals tested, up to 11 (24.4%) showed at least one response to peptide pools covering HIV Gag and Nef. A positive correlation was observed between the intensity (P = 0.0022) and magnitude (P = 0.0174) of the response detected in the HESN, and the viral load of the HIV-positive partner. Moreover, the result from the boosted flow and cytomix analyses showed a dominant Th1-like response pattern against HIV antigens, especially in CD8 T-cell populations.

Conclusions: The combined use of our boosted dendritic cell technique with a boosted flow cytometric approach allows us both to detect specific HIV-positive responses in a higher percentage of HESN patients and to define specific effector function profiles. This study contributes to a better understanding of resistance to HIV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Female
  • HIV Antigens / immunology*
  • HIV Infections / immunology*
  • HIV Seronegativity / immunology*
  • HIV-1 / immunology*
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Sexual Partners
  • Viral Load
  • Young Adult

Substances

  • HIV Antigens