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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2810-2817.
Prepublished online as a Blood First Edition Paper on July 1, 2004; DOI 10.1182/blood-2003-07-2314.


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Submitted July 10, 2003
Accepted June 9, 2004

HIV-1 infected dendritic cells upregulate cell surface markers but fail to produce IL-12 p70 in response to CD40ligand stimulation

Anna Smed-Sorensen*, Karin Lore, Lilian Walther-Jallow, Jan Andersson, and Anna-Lena Spetz

Department of Medicine, Center for Infectious Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
National Institutes of Health, Vaccine Research Center, Bethesda, Maryland, USA

* Corresponding author; email: anna.smed.sorensen{at}medhs.ki.se.

Dendritic cells (DCs) are antigen-presenting cells with the capacity to prime naive T cells for efficient cellular responses against pathogens such as HIV-1. DCs are also susceptible to HIV-1 infection, which may impair their ability to induce immunity. Here, we examined the ability of HIV-1 infected in vitro-derived DCs to respond to CD40ligand (CD40L) stimulation with the aim to study events during early HIV-1 infection. HIV-1BaL infected p24+ DCs were detected after only 3 days of exposure to highly concentrated virus. We show that HIV-1 infected DCs upregulated co-stimulatory molecules, but were skewed in their production of effector cytokines in response to CD40L stimulation. CD40L stimulation induced significant secretion of TNF{alpha} and IL-12 p70 from both HIV-1 exposed and unexposed DCs. Intracellular stainings of HIV-1 exposed DCs revealed that TNF{alpha} could be detected in both the p24- and p24+ DCs, but IL-12 p70 could only be found in the p24- DCs. Thus, while p24+ DCs showed a similar mature phenotype as p24- DCs after CD40L stimulation, they appeared to have an impaired cytokine profile. These observations suggest that HIV-1 infection disables DC function; a phenomenon that may be relevant for optimal induction of HIV-1 specific immune responses.


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