P18-08. Characterization of CD34+ derived dendritic cells generated in vitro and transfected with HIV gene as potential therapeutic vaccine in macaque

In this study, we demonstrate that the in vitro interactions between a CD56neg/CD16pos (CD56neg) subset of natural killer (NK) cells and autologous dendritic cells (DCs) from HIV-1–infected viremic but not aviremic individuals are markedly impaired and likely interfere with the development of an effective immune response. Among the defective interactions are abnormalities in the process of reciprocal NK–DC activation and maturation as well as a defect in the NK cell–mediated editing or elimination of immature DCs (iDCs). Notably, the lysis of mature DCs (mDCs) by autologous NK cells was highly impaired even after the complete masking of major histocompatibility complex I molecules, suggesting that the defective elimination of autologous iDCs is at the level of activating NK cell receptors. In this regard, the markedly impaired expression/secretion and function of NKp30 and TNF-related apoptosis-inducing ligand, particularly among the CD56neg NK cell subset, largely accounts for the highly defective NK cell–mediated lysis of autologous iDCs. Moreover, mDCs generated from HIV-1 viremic but not aviremic patients are substantially impaired in their ability to secrete interleukin (IL)-10 and -12 and to prime the proliferation of neighboring autologous NK cells, which, in turn, fail to secrete adequate amounts of interferon-γ.

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Characterization of the Phosphodiesterase (PDE) Pattern of in Vitro-Generated Human Dendritic Cells (DC) and the Influence of PDE Inhibitors on DC Function

Pulmonary Pharmacology & Therapeutics ◽

10.1006/pupt.1999.0220 ◽

1999 ◽

Vol 12 (6) ◽

pp. 377-386 ◽

Cited By ~ 31

Author(s):

Florian Gantner ◽

Christian Schudt ◽

Albrecht Wendel ◽

Armin Hatzelmann

Keyword(s):

Dendritic Cells ◽

Dc Function ◽

Pde Inhibitors ◽

Human Dendritic Cells

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Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells

Journal of Experimental Medicine ◽

10.1084/jem.20092618 ◽

2010 ◽

Vol 207 (6) ◽

pp. 1261-1271 ◽

Cited By ~ 471

Author(s):

Lionel Franz Poulin ◽

Mariolina Salio ◽

Emmanuel Griessinger ◽

Fernando Anjos-Afonso ◽

Ligia Craciun ◽

...

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Poly I:C ◽

Clinical Protocols ◽

Cell Responses ◽

Promising Target ◽

Important Player ◽

And Function

In mouse, a subset of dendritic cells (DCs) known as CD8α+ DCs has emerged as an important player in the regulation of T cell responses and a promising target in vaccination strategies. However, translation into clinical protocols has been hampered by the failure to identify CD8α+ DCs in humans. Here, we characterize a population of human DCs that expresses DNGR-1 (CLEC9A) and high levels of BDCA3 and resembles mouse CD8α+ DCs in phenotype and function. We describe the presence of such cells in the spleens of humans and humanized mice and report on a protocol to generate them in vitro. Like mouse CD8α+ DCs, human DNGR-1+ BDCA3hi DCs express Necl2, CD207, BATF3, IRF8, and TLR3, but not CD11b, IRF4, TLR7, or (unlike CD8α+ DCs) TLR9. DNGR-1+ BDCA3hi DCs respond to poly I:C and agonists of TLR8, but not of TLR7, and produce interleukin (IL)-12 when given innate and T cell–derived signals. Notably, DNGR-1+ BDCA3+ DCs from in vitro cultures efficiently internalize material from dead cells and can cross-present exogenous antigens to CD8+ T cells upon treatment with poly I:C. The characterization of human DNGR-1+ BDCA3hi DCs and the ability to grow them in vitro opens the door for exploiting this subset in immunotherapy.

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