Activation of a dendritic cell-T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells

doi:10.1084/jem.20081786

Published online
doi:10.1084/jem.20081786
The Journal of Experimental Medicine, Vol. 205, No. 12, 2717-2725
The Rockefeller University Press, 0022-1007 $30.00
© Perreau et al.

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BRIEF DEFINITIVE REPORT

Activation of a dendritic cell–T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells

Matthieu Perreau¹, Giuseppe Pantaleo¹^,2, and Eric J. Kremer³^,4

¹ Service of Immunology and Allergy, Department of Medicine, Centre Hospitalier, Universitaire Vaudois, Lausanne, University of Lausanne, CH-1011 Lausanne, Switzerland
² Swiss Vaccine Research Institute, 1011 Lausanne, Switzerland
³ Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique 5535, 34293 Montpellier, France
⁴ Université Montpellier I and II, 34967 Montpellier, France

CORRESPONDENCE Giuseppe Pantaleo: giuseppe.pantaleo{at}chuv.ch OR Eric J. Kremer: eric.kremer{at}igmm.cnrs.fr

The STEP HIV vaccine trial, which evaluated a replication-defectiveadenovirus type 5 (Ad5) vector vaccine, was recently stopped.The reasons for this included lack of efficacy of the vaccineand a twofold increase in the incidence of HIV acquisition amongvaccinated recipients with increased Ad5-neutralizing antibodytiters compared with placebo recipients. To model the eventsthat might be occurring in vivo, the effect on dendritic cells(DCs) of Ad5 vector alone or treated with neutralizing antiserum(Ad5 immune complexes [IC]) was compared. Ad5 IC induced morenotable DC maturation, as indicated by increased CD86 expression,decreased endocytosis, and production of tumor necrosis factorand type I interferons. We found that DC stimulation by Ad5IC was mediated by the Fc ${gamma}$ receptor IIa and Toll-like receptor9 interactions. DCs treated with Ad5 IC also induced significantlyhigher stimulation of Ad5-specific CD8 T cells equipped withcytolytic machinery. In contrast to Ad5 vectors alone, Ad5 ICcaused significantly enhanced HIV infection in DC–T cellcocultures. The present results indicate that Ad5 IC activatesa DC–T cell axis that, together with the possible persistenceof the Ad5 vaccine in seropositive individuals, may set up apermissive environment for HIV-1 infection, which could accountfor the increased acquisition of HIV-1 infection among Ad5 seropositivevaccine recipients.

© 2008 Perreau et al. This article is distributed underthe terms of an Attribution–Noncommercial–ShareAlike–No Mirror Sites license for the first six monthsafter the publication date (see http://www.jem.org/misc/terms.shtml).After six months it is available under a Creative Commons License(Attribution–Noncommercial–Share Alike 3.0 Unportedlicense, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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