HIV-1-infected dendritic cells up-regulate cell surface markers but fail to produce IL-12 p70 in response to CD40 ligand stimulation.
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-1(BaL)-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 alpha (TNFalpha) and interleukin 12 (IL-12) p70 from both HIV-1-exposed and unexposed DCs. Intracellular stainings of HIV-1-exposed DCs revealed that TNFalpha 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.
Smed-Sörensen
Anna
A
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, F59 Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. anna.smed.sorensen@medhs.ki.se
Loré
Karin
K
Walther-Jallow
Lilian
L
Andersson
Jan
J
Spetz
Anna-Lena
AL
D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis*; D051940:B7-2 Antigen; D023201:CD40 Ligand / Q000276:immunology / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis; D021122:Protein Subunits / Q000096:biosynthesis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D015703:Antigens, CD; D018949:Antigens, CD1; D000954:Antigens, Surface; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D016655:HIV Core Protein p24; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D018664:Interleukin-12