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Volume 9 Supplement 2

AIDS Vaccine 2012

  • Poster presentation
  • Open Access

HIV-1 capture and antigen presentation by dendritic cells: enhanced viral capture does not correlate with better T-Cell activation

  • 1,
  • 2,
  • 2,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 2,
  • 1,
  • 1,
  • 3 and
  • 1
Retrovirology20129 (Suppl 2) :P2

https://doi.org/10.1186/1742-4690-9-S2-P2

  • Published:

Keywords

  • Dendritic Cell
  • Antigen Presentation
  • Dendritic Cell Maturation
  • Immature Dendritic Cell
  • Mature Dendritic Cell

Background

During HIV-1 infection, dendritic cells (DC) facilitate dissemination of HIV-1 while trying to trigger adaptive antiviral immune responses. We examined whether increased HIV-1 capture in DC matured with lipopolysaccharide (LPS) results in more efficient antigen presentation to HIV-1–specific CD4+ and CD8+ T cells. In order to block the DC-mediated trans-infection of HIV-1 and maximize antigen loading, we also evaluated a non-infectious integrase-deficient HIV-1 isolate, the HIVNL4-3ΔIN.

Methods

Immature DC (iDC), mature DC (mDC) activated with IL-1β, TNF-α, IL-6, and PGE2 (ITIP) or LPS during viral uptake, and fully mDC matured with ITIP or with LPS for 48 h before viral loading were tested. Antigen presentation to HIV-1-specific CD4+ and CD8+ T cell clones was quantified by IFN-γ ELISPOT. DC-associated p24Gag HIV-1 and DC-mediated HIV-1 trans-infection were also evaluated in parallel.

Results

We showed that higher viral capture of DC did not guarantee better antigen presentation or T-cell activation. Greater HIVNL4-3 uptake by fully LPS-matured DC resulted in higher viral transmission to target cells but poorer stimulation of HIV-1–specific CD4+ and CD8+ T cells. Conversely, maturation of DC with LPS during—but not before—viral loading enhanced both HLA-I and HLA-II HIV-1–derived antigen presentation. On the other hand, DC maturation with ITIP during viral uptake only stimulated HIV-1–specific CD8+ T cells. Integrase-deficient HIVNL4-3ΔIN was also efficiently captured and presented by DC through HLA-I and HLA-II pathways, but in absence of viral dissemination.

Conclusion

Hence, DC maturation state, activation stimulus, and time lag between DC maturation and antigen loading impact HIV-1 capture and virus antigen presentation. Our results demonstrate a dissociation between the capacity to capture HIV-1 and to present viral antigens. HIVNL4-3ΔIN seems to be an attractive candidate to be explored. These results provide new insights into DC biology and have implications in the optimization of DC-based immunotherapy against HIV-1 infection.

Authors’ Affiliations

(1)
AIDS Research Institute IrsiCaixa, Badalona, Spain
(2)
INSERM, UMRS-945, Infection and Immunity, Université Pierre et Marie C, Paris, France
(3)
INSERM, UMRS-945, Infection and Immunity, Univ. Pierre et Marie Curie, Paris, France

Copyright

© Rodriguez-Plata et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://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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