Maturation of dendritic cells for enhanced activation of anti-HIV-1 CD8(+) T cell immunity.

TitleMaturation of dendritic cells for enhanced activation of anti-HIV-1 CD8(+) T cell immunity.
Publication TypeJournal Article
Year of Publication2008
AuthorsHuang X-L, Fan Z, Borowski L, Rinaldo CR
JournalJ Leukoc Biol
Volume83
Issue6
Pagination1530-40
Date Published2008 Jun
ISSN0741-5400
KeywordsAcquired Immunodeficiency Syndrome, CD40 Ligand, CD8-Positive T-Lymphocytes, Dendritic Cells, HIV-1, Humans, Interferon-gamma, Interleukin-12, Lymphocyte Activation, Toll-Like Receptor 3
Abstract

Maturation of dendritic cells (DC) to enhance their capacity to activate T cell immunity to HIV-1 is a key step in immunotherapy of HIV-1 infection with DC. We compared maturation of DC derived from HIV-1-uninfected subjects and infected subjects on antiretroviral therapy (ART) or ART naïve by CD40 ligand (CD40L) and combinations of TLR3 ligand polyinosinic:polycytidylic acid [poly(I:C)] and inflammatory cytokines IFN-gamma, IFN-alpha, IL-1beta, and TNF-alpha. The greatest levels of virus-specific IFN-gamma production by CD8(+) T cells were stimulated by DC treated with CD40L, followed by DC treated with the poly(I:C)-cytokine combination. The highest levels of IL-12p70 were produced by DC treated with CD40L + IFN-gamma, followed by CD40L and the poly(I:C)-cytokine combination. Neutralization of IL-12p70 indicated that it was only partially involved in direct enhancement of antiviral CD8(+) T cell activity. DC stimulation of antiviral CD8(+) T cell reactivity was enhanced by activated CD4(+) T cells at low concentrations but was suppressed at higher CD4(+) T cell concentrations. Maturation of DC with CD40L obviated the need for CD4(+) T cell help and overcame this suppressive activity. Finally, we showed that DC from HIV-1-infected subjects on ART, which were treated with the poly(I:C)-cytokine combination, retained the capacity to produce IL-12p70 and activate anti-HIV-1 CD8(+) T cell responses after restimulation with CD40L, with or without IFN-gamma. Thus, DC from HIV-1-infected subjects can be engineered with CD40L or a poly(I:C)-cytokine combination for enhancing CD8(+) T cell responses to HIV-1, which has potential applications in HIV-1 immunotherapy.

DOI10.1189/jlb.1107795
Alternate JournalJ. Leukoc. Biol.
PubMed ID18364435
Grant ListP01 AI 055794 / AI / NIAID NIH HHS / United States
R37 AI 41870 / AI / NIAID NIH HHS / United States
R37 AI041870 / AI / NIAID NIH HHS / United States
U01 AI 35041 / AI / NIAID NIH HHS / United States