HIV-1-infected dendritic cells up-regulate cell surface markers but fail to produce IL-12 p70 in response to CD40 ligand stimulation

• Published in: Blood 2004-11, Vol.104 (9), p.2810-2817
• Main Authors: Smed-Sörensen, Anna, Loré, Karin, Walther-Jallow, Lilian, Andersson, Jan, Spetz, Anna-Lena
• Format: Article
• Language: English
• Subjects: Antigens, CD - analysis; Antigens, CD1 - analysis; Antigens, Surface - analysis; B7-2 Antigen; Biological and medical sciences; CD40 Ligand - immunology; CD40 Ligand - pharmacology; Cells, Cultured; Cytokines - metabolism; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - virology; HIV Core Protein p24 - analysis; HIV Infections - immunology; HIV-1; Human viral diseases; Humans; Immunophenotyping; Infectious diseases; Interleukin-12 - biosynthesis; Interleukin-12 - metabolism; Medical sciences; Medicin och hälsovetenskap; Membrane Glycoproteins - analysis; Protein Subunits - biosynthesis; Protein Subunits - metabolism; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-07-2314

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 CD40 ligand (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 up-regulated costimulatory molecules, but were skewed in their production of effector cytokines in response to CD40L stimulation. CD40L stimulation induced significant secretion of tumor necrosis factor α (TNFα) and interleukin 12 (IL-12) p70 from both HIV-1-exposed and unexposed DCs. Intracellular stainings of HIV-1-exposed DCs revealed that TNFα could be detected in both the p24- and p24+ DCs, but IL-12 p70 could be found only in the p24- DCs. Thus, although p24+ DCs showed a mature phenotype similar to 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. (Blood. 2004;104:2810-2817)