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Primary human immunodeficiency virus type 1-specific CD8+ T-cell responses induced by myeloid dendritic cells.

Journal of virology (2009-04-10)
Bonnie A Colleton, Xiao-Li Huang, Nada M Melhem, Zheng Fan, Luann Borowski, Giovanna Rappocciolo, Charles R Rinaldo
ABSTRACT

Induction of an antigenically broad and vigorous primary T-cell immune response by myeloid dendritic cells (DC) in blood and tissues could be important for an effective prophylactic or therapeutic vaccine to human immunodeficiency virus type 1 (HIV-1). Here we show that a primary CD8(+) T-cell response can be induced by HIV-1 peptide-loaded DC derived from blood monocytes of HIV-1-negative adults and neonates (moDC) and by Langerhans cells (LC) and interstitial, dermal-intestinal DC (idDC) derived from CD34(+) stem cells of neonatal cord blood. Optimal priming of single-cell gamma interferon (IFN-gamma) production by CD8(+) T cells required CD4(+) T cells and was broadly directed to multiple regions of Gag, Env, and Nef that corresponded to known and predicted major histocompatibility complex class I epitopes. Polyfunctional CD8(+) T-cell responses, defined as single-cell production of more than one cytokine (IFN-gamma, interleukin 2, or tumor necrosis factor alpha), chemokine (macrophage inhibitory factor 1beta), or cytotoxic degranulation marker CD107a, were primed by moDC, LC, and idDC to HIV-1 Gag and reverse transcriptase epitopes, as well as to Epstein-Barr virus and influenza A virus epitopes. Thus, three major types of blood and tissue myeloid DC targeted by HIV-1, i.e., moDC, LC, and idDC, can prime multispecific, polyfunctional CD8(+) T-cell responses to HIV-1 and other viral antigens.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Human Serum, from human male AB plasma, USA origin, sterile-filtered
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Brefeldin A, ≥99% (HPLC and TLC), BioXtra, for molecular biology
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Human Serum, Heat Inactivated (from male AB clotted whole blood), USA origin, sterile-filtered
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Brefeldin A, from Penicillium brefeldianum, Ready Made Solution, 10 mg/mL in DMSO
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