Dendritic cell amplification of HIV type 1-specific CD8+ T cell responses in exposed, seronegative heterosexual women

Barbara Shacklett, Donald B. Louria, Douglas F. Nixon, Robert E. Means, Marie Larsson, David T. Wilkens, Thomas J. Beadle, Melissa J. Merritt, Nina Bhardwaj, Paul E. Palumbo, Joan H. Skurnick

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

In the Heterosexual AIDS Transmission Study (HATS), the frequency of high-risk sexual activity and viral load in the seropositive partner were shown to correlate with HIV-1 transmission. However, these parameters could not account for the status of some exposed, seronegative (ESN) individuals who remained uninfected despite years of exposure. To test the hypothesis that antiviral immune responses are a correlate of nontransmission in this cohort, we developed two sensitive methods for assessing HIV-1-specific humoral and cell-mediated responses. To quantify T cell responses, autologous mature dendritic cells (DCs) were used as antigen-presenting cells to elicit HIV-1-specific IFN-γ production by ELISPOT. Antibody responses to HIV-1 gp120 were assessed by combination immunoprecipitation-Western blot (IP-WB). Previous studies of this cohort, using limiting dilution analysis, did not reveal HIV-1-specific cytotoxic T lymphocyte activity. However, when autologous DCs were used to present HIV-1 antigens, T cells from three of eight ESN women (38%) responded by producing IFN-γ. T cells from three of four seropositive partners responded to HIV-1 antigens, whereas five negative controls did not. The use of DCs as antigen-presenting cells increased sensitivity by 2- to 30-fold relative to standard ELISPOT. Using IP-WB, low levels of gp120-reactive antibodies were detected in plasma from 1 of 14 ESN women. These results support the hypothesis that HIV-1-specific T cell responses play a role in immune surveillance in this cohort of North American serodiscordant couples. This report also demonstrates the ability of dendritic cells to reveal T cell responses that might be overlooked by other methods.

Original languageEnglish (US)
Pages (from-to)805-815
Number of pages11
JournalAIDS Research and Human Retroviruses
Volume18
Issue number11
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Immunology
  • Virology

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