In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 83, No. 6 ( 2008-06-01), p. 1530-1540
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-γ, IFN-α, IL-1β, and TNF-α. The greatest levels of virus-specific IFN-γ 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-γ, 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-γ. 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.
Type of Medium:
Online Resource
ISSN:
0741-5400
,
1938-3673
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2008
detail.hit.zdb_id:
2026833-6
SSG:
12
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