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

2010 ◽  
Vol 207 (6) ◽  
pp. 1261-1271 ◽  
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.

scholarly journals Endogenous dendritic cells mediate the effects of intravenously injected therapeutic immunosuppressive dendritic cells in transplantation

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2694-2705 ◽  
Author(s):  
Sherrie J. Divito ◽  
Zhiliang Wang ◽  
William J. Shufesky ◽  
Quan Liu ◽  
Olga A. Tkacheva ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Indirect Pathway ◽  
Allograft Survival ◽  
Complex Molecules ◽  
Cell Responses ◽  
Histocompatibility Complex

Abstract The prevailing idea regarding the mechanism(s) by which therapeutic immunosuppressive dendritic cells (DCs) restrain alloimmunity is based on the concept that they interact directly with antidonor T cells, inducing anergy, deletion, and/or regulation. However, this idea has not been tested in vivo. Using prototypic in vitro–generated maturation-resistant (MR) DCs, we demonstrate that once MR-DCs carrying donor antigen (Ag) are administered intravenously, they decrease the direct and indirect pathway T-cell responses and prolong heart allograft survival but fail to directly regulate T cells in vivo. Rather, injected MR-DCs are short-lived and reprocessed by recipient DCs for presentation to indirect pathway CD4+ T cells, resulting in abortive activation and deletion without detrimental effect on the number of indirect CD4+ FoxP3+ T cells, thus increasing the regulatory to effector T cell relative percentage. The effect on the antidonor response was independent of the method used to generate therapeutic DCs or their viability; and in accordance with the idea that recipient Ag-presenting cells mediate the effects of therapeutic DCs in transplantation, prolongation of allograft survival was achieved using donor apoptotic MR-DCs or those lacking surface major histocompatibility complex molecules. We therefore conclude that therapeutic DCs function as Ag-transporting cells rather than Ag-presenting cells to prolong allograft survival.

scholarly journals Aggregation of Human Recombinant Monoclonal Antibodies Influences the Capacity of Dendritic Cells to Stimulate Adaptive T-Cell Responses In Vitro

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e86322 ◽  
Author(s):  
Verena Rombach-Riegraf ◽  
Anette C. Karle ◽  
Babette Wolf ◽  
Laetitia Sordé ◽  
Stephan Koepke ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses

Enhanced in vitro stimulation of rhesus macaque dendritic cells for activation of SIV-specific T cell responses

2002 ◽  
Vol 260 (1-2) ◽  
pp. 219-234 ◽  
Author(s):  
Erin Mehlhop ◽  
Loreley A. Villamide ◽  
Ines Frank ◽  
Agegnehu Gettie ◽  
Christine Santisteban ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Rhesus Macaque ◽  
T Cell Responses ◽  
Cell Responses ◽  
Stimulation Of

Dendritic cells overexpressing CD95 (Fas) ligand elicit vigorous allospecific T-cell responses in vivo

Blood ◽  
2003 ◽  
Vol 101 (4) ◽  
pp. 1469-1476 ◽  
Author(s):  
Sofia Buonocore ◽  
Frédéric Paulart ◽  
Alain Le Moine ◽  
Michel Braun ◽  
Isabelle Salmon ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Fas Ligand ◽  
T Cell Responses ◽  
Genetically Engineered ◽  
Peripheral Tolerance ◽  
Cytotoxic T Cell ◽  
Cell Responses

Dendritic cells (DCs) genetically engineered to overexpress CD95 (Fas) ligand (CD95L-DC) were proposed as tools to induce peripheral tolerance to alloantigens. Herein, we observed that CD95L-DC obtained after retroviral gene transfer in bone marrow (BM) precursors derived from CD95-deficient (lpr/lpr) mice elicit much stronger allospecific type 1 helper T-cell and cytotoxic T-cell activities than control DCs upon injection in vivo, although they induce lower T-cell responses in vitro. Indeed, a single injection of CD95L-DC prepared from C57BL/6 mice was sufficient to prime bm13 recipients for acute rejection of C57BL/6 skin allografts that were otherwise tolerated in the context of this single weak major histocompatibility complex (MHC) class I incompatibility. Massive neutrophil infiltrates depending on interleukin (IL)–1 signaling were observed at sites of CD95L-DC injection. Experiments in IL-1 receptor–deficient mice or in animals injected with depleting anti-Gr1 monoclonal antibody (mAb) established that neutrophil recruitment is required for the development of vigorous T-cell responses after injection of CD95L-DC in vivo.

Dendritic Cells Reconstituted with a Human Heparanase Gene Induce Potent Cytotoxic T-Cell Responses against Gastric Tumor Cells in vitro

Tumor Biology ◽  
2007 ◽  
Vol 28 (4) ◽  
pp. 238-246 ◽  
Author(s):  
Yong-Guo Cai ◽  
Dian-Chun Fang ◽  
Ling Chen ◽  
Xu-Dong Tang ◽  
Ting Chen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Tumor Cells ◽  
T Cell Responses ◽  
Gastric Tumor ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses

scholarly journals Characterization of the defective interaction between a subset of natural killer cells and dendritic cells in HIV-1 infection

2006 ◽  
Vol 203 (10) ◽  
pp. 2339-2350 ◽  
Author(s):  
Domenico Mavilio ◽  
Gabriella Lombardo ◽  
Audrey Kinter ◽  
Manuela Fogli ◽  
Andrea La Sala ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Subset ◽  
Interferon Γ ◽  
And Function ◽  
Hiv 1

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.

scholarly journals Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: a model for HIV immunopathogenesis

Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5152-5162 ◽  
Author(s):  
Adriano Boasso ◽  
Caroline M. Royle ◽  
Spyridon Doumazos ◽  
Veronica N. Aquino ◽  
Mara Biasin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Interaction ◽  
Type I ◽  
Cell Responses ◽  
Hiv Exposed ◽  
Antigen Presenting ◽  
Hiv Envelope

AbstractA delicate balance between immunostimulatory and immunosuppressive signals mediated by dendritic cells (DCs) and other antigen-presenting cells (APCs) regulates the strength and efficacy of antiviral T-cell responses. HIV is a potent activator of plasmacytoid DCs (pDCs), and chronic pDC activation by HIV promotes the pathogenesis of AIDS. Cholesterol is pivotal in maintaining HIV envelope integrity and allowing HIV-cell interaction. By depleting envelope-associated cholesterol to different degrees, we generated virions with reduced ability to activate pDCs. We found that APC activation was dissociated from the induction of type I IFN-α/β and indoleamine-2,3-dioxygenase (IDO)–mediated immunosuppression in vitro. Extensive cholesterol withdrawal, resulting in partial protein and RNA loss from the virions, rendered HIV a more powerful recall immunogen for stimulating memory CD8 T-cell responses in HIV-exposed, uninfected individuals. These enhanced responses were dependent on the inability of cholesterol-depleted HIV to induce IFN-α/β.

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