The Experts below are selected from a list of 8232 Experts worldwide ranked by ideXlab platform
Angus W Thomson - One of the best experts on this subject based on the ideXlab platform.
-
circulating Dendritic Cell Subset levels after allogeneic stem Cell transplantation in children correlate with time post transplant and severity of acute graft versus host disease
Bone Marrow Transplantation, 2005Co-Authors: J Vakkila, Angus W Thomson, Liisa Hovi, Kim Vettenranta, Ulla M SaarinenpihkalaAbstract:Circulating Dendritic Cell Subset levels after allogeneic stem Cell transplantation in children correlate with time post transplant and severity of acute graft-versus-host disease
-
Dendritic Cell Subset ratio in tolerant weaning and non tolerant liver recipients is not affected by extent of immunosuppression
Transplantation, 2004Co-Authors: George V Mazariegos, Alan F Zahorchak, J Reyes, Adriana Zeevi, Holly Chapman, Angus W ThomsonAbstract:Dendritic Cell (DC) Subsets regulate alloimmune responses and may play a role in transplant tolerance. We extend an analysis of circulating precursors (p) of CD11c(+) CD123(-/lo) (IL-3Ralpha(-/lo)) (pDC1) and CD11c(-) CD123(hi) (pDC2) DC Subsets in primary cadaveric liver allograft recipients. Additionally, we examine DC Subset levels in relation to the nature and extent of immunosuppressive therapy. The data consolidate the finding that the pDC2/pDC1 Subset ratio is significantly higher in patients on minimal calcineurin inhibitor monotherapy undergoing successful weaning (n = 36) and in those off all anti-rejection therapy (n = 18) compared with patients on maintenance immunosuppression (n = 21). No relationship was found between the incidence of either pDC Subset or the pDC Subset ratio and time post-transplant or time off immunosuppression in any group. There was also no correlation between the pDC Subset ratio and either prednisone or tacrolimus dose or tacrolimus trough blood level. No evidence was found that combination of these drugs influenced the incidence of pDC2 relative to pDC1. Thus, a greater prevalence of pDC2 in stable liver recipients on low dose anti-rejection therapy or in those off immunosuppression, compared with that in patients on maintenance immunosuppression, does not reflect a differential effect of anti-rejection drugs on pDC Subsets.
-
Dendritic Cell Subset ratio in peripheral blood correlates with successful withdrawal of immunosuppression in liver transplant patients
American Journal of Transplantation, 2003Co-Authors: George V Mazariegos, Alan F Zahorchak, J Reyes, L Ostrowski, Bridget Flynn, Adriana Zeevi, Angus W ThomsonAbstract:Human Dendritic Cell (DC) Subsets appear to play distinct roles in the induction and regulation of immune responses. While monocytoid DC (DC1) induce T-helper (Th) 1-type responses, plasmacytoid DC (DC2) have been reported to selectively induce Th2 responses. In blood, their precursors (p) can be identified as HLA-DR+ lineage– Cells that are further characterized as CD11c+ CD123–/lo (IL-3Rα–/lo) (pDC1) or as CD11c– CD123hi (pDC2) by rare event, flow cytometric analysis. We compared the incidences of pDC1 and pDC2 in peripheral blood mononuclear Cell populations isolated from normal healthy controls and from 3 groups of clinically stable liver transplant patients. Group A had been successfully withdrawn from immunosuppression, whereas group B were undergoing prospective drug weaning and on minimal anti-rejection therapy. In group C, drug withdrawal had either failed or never been attempted and patients were on maintenance immunosuppression. Assessment of DC Subsets and the pDC2 : pDC1 ratio showed good intra-and interassay reproducibility. Compared with patients in group C, those in groups A and B demonstrated a significantly higher relative incidence of pDC2 and a lower incidence of pDC1 – similar to those values observed in normal healthy controls. Moreover, the pDC2 : pDC1 ratio was significantly higher in patients undergoing (successful) weaning and in those off immunosuppression compared with patients on maintenance immunosuppression.
Kayo Inaba - One of the best experts on this subject based on the ideXlab platform.
-
langerhans Cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling
The Journal of Allergy and Clinical Immunology, 2012Co-Authors: Saeko Nakajima, Steven F Ziegler, Botond Z Igyarto, Tetsuya Honda, Gyohei Egawa, Atsushi Otsuka, Mariko Harachikuma, Norihiko Watanabe, Michio Tomura, Kayo InabaAbstract:Background The clarification of cutaneous Dendritic Cell Subset and the role of thymic stromal lymphopoietin (TSLP) signaling in epicutaneous sensitization with protein antigens, as in the development of atopic dermatitis, is a crucial issue. Objectives Because TSLP is highly expressed in the vicinity of Langerhans Cells (LCs), we sought to clarify our hypothesis that LCs play an essential role in epicutaneous sensitization with protein antigens through TSLP signaling. Methods By using Langerin-diphtheria toxin receptor knock-in mice and human Langerin-diphtheria toxin A transgenic mice, we prepared mice deficient in LCs. We also prepared mice deficient in TSLP receptors in LCs by using TSLP receptor–deficient mice with bone marrow chimeric technique. We applied these mice to an ovalbumin (OVA)-induced epicutaneous sensitization model. Results Upon the epicutaneous application of OVA, conditional LC depletion attenuated the development of clinical manifestations as well as serum OVA-specific IgE increase, OVA-specific T-Cell proliferation, and IL-4 mRNA expression in the draining lymph nodes. Consistently, even in the steady state, permanent LC depletion resulted in decreased serum IgE levels, suggesting that LCs mediate the T H 2 local environment. In addition, mice deficient in TSLP receptors on LCs abrogated the induction of OVA-specific IgE levels upon epicutaneous OVA sensitization. Conclusion LCs initiate epicutaneous sensitization with protein antigens and induce T H 2-type immune responses via TSLP signaling.
-
th2 dominance and defective development of a cd8 Dendritic Cell Subset in id2 deficient mice
The Journal of Allergy and Clinical Immunology, 2003Co-Authors: Takashi Kusunoki, Tomonori Iyoda, Yoshiki Omatsu, Kayo Inaba, Manabu Sugai, Tomoya Katakai, Tatsutoshi Nakahata, Akira Shimizu, Yoshifumi YokotaAbstract:Abstract Background: Although the T H 1/T H 2 balance is important in many clinical situations, the regulatory mechanisms in vivo have not been well elucidated. Objective: We sought to characterize the immunologic status of mice lacking Id2, an inhibitor of basic helix-loop-helix transcription factors. Methods: We analyzed serum immunoglobulin levels, gene-expression profiles in the spleen, T H 1/T H 2 balance, and Dendritic Cell (DC) populations of Id2 –/– mice. Results: Serum levels of T H 2-mediated IgG1 and IgE were increased more than 10-fold in Id2 –/– mice without antigenic stimulation. Gene-expression analysis in Id2 –/– splenocytes revealed enhanced expression of T H 2-related genes, such as IL-4, and reduced expression of T H 1-related genes, including IFN-γ and IL-12. IntraCellular cytokine staining also confirmed that Id2 –/– splenic CD4 + T Cells are substantially skewed to T H 2 Cells. However, Id2 –/– naive CD4 + T Cells differentiated into T H 1 Cells comparably with wild-type T Cells under the appropriate culture conditions. Id2 –/– mice displayed a selective and remarkable reduction of the CD8α + DC Subset, which is known to induce preferential T H 1 differentiation. Conclusion: Id2 is an indispensable regulator of the T H 1/T H 2 balance, possibly through the proper development of CD8α + DCs, and could be a novel target to treat allergic diseases. J Allergy Clin Immunol 2003;111:136-42.
-
the cd8 Dendritic Cell Subset selectively endocytoses dying Cells in culture and in vivo
Journal of Experimental Medicine, 2002Co-Authors: Tomonori Iyoda, Susumu Shimoyama, Kang Liu, Yoshiki Omatsu, Yuji Akiyama, Yasuhiro Maeda, Kazuhiko Takahara, Ralph M Steinman, Kayo InabaAbstract:Dendritic Cells (DCs) are able in tissue culture to phagocytose and present antigens derived from infected, malignant, and allogeneic Cells. Here we show directly that DCs in situ take up these types of Cells after fluorescent labeling with carboxyfluorescein succinimidyl ester (CFSE) and injection into mice. The injected Cells include syngeneic splenocytes and tumor Cell lines, induced to undergo apoptosis ex vivo by exposure to osmotic shock, and allogeneic B Cells killed by NK Cells in situ. The CFSE-labeled Cells in each case are actively endocytosed by DCs in vivo, but only the CD8+ Subset. After uptake, all of the phagocytic CD8+ DCs can form major histocompatibility complex class II–peptide complexes, as detected with a monoclonal antibody specific for these complexes. The CD8+ DCs also selectively present Cell-associated antigens to both CD4+ and CD8+ T Cells. Similar events take place with cultured DCs; CD8+ DCs again selectively take up and present dying Cells. In contrast, both CD8+ and CD8− DCs phagocytose latex particles in culture, and both DC Subsets present soluble ovalbumin captured in vivo. Therefore CD8+ DCs are specialized to capture dying Cells, and this helps to explain their selective ability to cross present Cellular antigens to both CD4+ and CD8+ T Cells.
Artur Paiva - One of the best experts on this subject based on the ideXlab platform.
-
alterations in peripheral blood monocyte and Dendritic Cell Subset homeostasis in relapsing remitting multiple sclerosis patients
Journal of Neuroimmunology, 2021Co-Authors: Andreia Monteiro, Pedro Rosado, Luiza Rosado, Ana Mafalda Fonseca, Margarida Coucelo, Artur PaivaAbstract:Antigen-presenting Cells participate and are implicated in the pathogenesis of multiple sclerosis. In our study we assessed the frequency of plasmacytoid (pDC) and myeloid (mDC) Dendritic Cells and the classical, intermediate and non-classical monocytes Subsets, as well as their phenotypic and functional profile. We evaluated peripheral blood from relapsing-remitting patients treated with IFN-β in remission and relapse phases and from healthy subjects. In remission, we observed a decrease of mDC/pDC ratio and a return to normal values in relapse. In both phases the frequency of non-classical monocytes decreases. Concerning the phenotypic characterization, an increased HLA-DR expression was observed in remission and a decrease in relapse, revealing alterations in monocytes and Dendritic Cells homeostasis.
David Sancho - One of the best experts on this subject based on the ideXlab platform.
-
Effective cancer immunotherapy by natural mouse conventional type-1 Dendritic Cells bearing dead tumor antigen
BMC, 2019Co-Authors: Stefanie K. Wculek, Joaquín Amores-iniesta, Ruth Conde-garrosa, Sofía C. Khouili, Ignacio Melero, David SanchoAbstract:Abstract Background The manipulation of Dendritic Cells (DCs) for cancer vaccination has not reached its full potential, despite the revolution in cancer immunotherapy. DCs are fundamental for CD8+ T Cell activation, which relies on cross-presentation of exogenous antigen on MHC-I and can be fostered by immunogenic cancer Cell death. Translational and clinical research has focused on in vitro-generated monocyte-derived DCs, while the vaccination efficacy of natural conventional type 1 DCs (cDC1s), which are associated with improved anti-tumor immunity and specialize on antigen cross-presentation, remains unknown. Methods We isolated primary spleen mouse cDC1s and established a protocol for fast ex vivo activation and antigen-loading with lysates of tumor Cells that underwent immunogenic Cell death by UV irradiation. Natural tumor antigen-loaded cDC1s were transferred and their potential for induction of endogenous CD8+ and CD4+ T Cell responses in vivo, cancer prevention and therapy were assessed in three grafted cancer models. Further, we tested the efficacy of natural cDC1 vaccination in combination and comparison with anti-PD-1 treatment in two “wildtype” tumor models not expressing exogenous antigens. Results Herein, we reveal that primary mouse cDC1s ex vivo loaded with dead tumor Cell-derived antigen are activated and induce strong CD8+ T Cell responses from the endogenous repertoire upon adoptive transfer in vivo through tumor antigen cross-presentation. Notably, cDC1-based vaccines enhance tumor infiltration by cancer-reactive CD8+ and CD4+ T Cells and halt progression of engrafted cancer models, including tumors that are refractory to anti-PD-1 treatment. Moreover, combined tumor antigen-loaded primary cDC1 and anti-PD-1 therapy had strong synergistic effects in a PD-1 checkpoint inhibition susceptible cancer model. Conclusions This preclinical proof-of-principle study is first to support the therapeutic efficacy of cancer immunotherapy with syngeneic dead tumor Cell antigen-loaded mouse cDC1s, the equivalents of the human Dendritic Cell Subset that correlates with beneficial prognosis of cancer patients. Our data pave the way for translation of cDC1-based cancer treatments into the clinic when isolation of natural human cDC1s becomes feasible
-
identification of a Dendritic Cell receptor that couples sensing of necrosis to immunity
Nature, 2009Co-Authors: David Sancho, Olivier Joffre, Anna M Keller, Neil C Rogers, Dolores Martinez, Patricia Hernanzfalcon, Ian Rosewell, Caetano Reis E SousaAbstract:Necrotic Cell corpses accumulate in tissues as a result of injury or impaired clearance of apoptotic Cells, and can induce an inflammatory response that initiates tissue repair. The recently described Dendritic C-type lectin receptor CLEC9A, also called DNGR-1, is shown to sense necrotic debris by recognizing a preformed signal that is exposed on necrotic Cells, and to mediate cross presentation of dead Cell-associated antigens. This study shows that Dendritic Cells use the C-type lectin CLEC9A to sense necrotic Cell debris and to mediate cross-presentation of dead-Cell-associated antigens. Injury or impaired clearance of apoptotic Cells leads to the pathological accumulation of necrotic corpses, which induce an inflammatory response that initiates tissue repair1. In addition, antigens present in necrotic Cells can sometimes provoke a specific immune response2,3,4 and it has been argued that necrosis could explain adaptive immunity in seemingly infection-free situations, such as after allograft transplantation or in spontaneous and therapy-induced tumour rejection5,6. In the mouse, the CD8α+ Subset of Dendritic Cells phagocytoses dead Cell remnants and cross-primes CD8+ T Cells against Cell-associated antigens7. Here we show that CD8α+ Dendritic Cells use CLEC9A (also known as DNGR-1), a recently-characterized C-type lectin8,9,10, to recognize a preformed signal that is exposed on necrotic Cells. Loss or blockade of CLEC9A does not impair the uptake of necrotic Cell material by CD8α+ Dendritic Cells, but specifically reduces cross-presentation of dead-Cell-associated antigens in vitro and decreases the immunogenicity of necrotic Cells in vivo. The function of CLEC9A requires a key tyrosine residue in its intraCellular tail that allows the recruitment and activation of the tyrosine kinase SYK, which is also essential for cross-presentation of dead-Cell-associated antigens. Thus, CLEC9A functions as a SYK-coupled C-type lectin receptor to mediate sensing of necrosis by the principal Dendritic-Cell Subset involved in regulating cross-priming to Cell-associated antigens.
-
identification of a Dendritic Cell receptor that couples sensing of necrosis to immunity
Nature, 2009Co-Authors: David Sancho, Olivier Joffre, Anna M Keller, Neil C Rogers, Dolores Martinez, Patricia Hernanzfalcon, Ian Rosewell, Caetano Reis E SousaAbstract:Injury or impaired clearance of apoptotic Cells leads to the pathological accumulation of necrotic corpses, which induce an inflammatory response that initiates tissue repair. In addition, antigens present in necrotic Cells can sometimes provoke a specific immune response and it has been argued that necrosis could explain adaptive immunity in seemingly infection-free situations, such as after allograft transplantation or in spontaneous and therapy-induced tumour rejection. In the mouse, the CD8alpha+ Subset of Dendritic Cells phagocytoses dead Cell remnants and cross-primes CD8+ T Cells against Cell-associated antigens. Here we show that CD8alpha+ Dendritic Cells use CLEC9A (also known as DNGR-1), a recently-characterized C-type lectin, to recognize a preformed signal that is exposed on necrotic Cells. Loss or blockade of CLEC9A does not impair the uptake of necrotic Cell material by CD8+ Dendritic Cells, but specifically reduces cross-presentation of dead-Cell-associated antigens in vitro and decreases the immunogenicity of necrotic Cells in vivo. The function of CLEC9A requires a key tyrosine residue in its intraCellular tail that allows the recruitment and activation of the tyrosine kinase SYK, which is also essential for cross-presentation of dead-Cell-associated antigens. Thus, CLEC9A functions as a SYK-coupled C-type lectin receptor to mediate sensing of necrosis by the principal Dendritic-Cell Subset involved in regulating cross-priming to Cell-associated antigens.
Ronald N. Germain - One of the best experts on this subject based on the ideXlab platform.
-
Dendritic Cell Subset positioning governs clonal diversity and magnitude of the cd8 t Cell response
Journal of Immunology, 2016Co-Authors: Michael Y Gerner, Wolfgang Kastenmuller, Ronald N. GermainAbstract:Although the molecular requirements for CD8 T Cell responses have been well characterized, subunit vaccine formulations struggle to generate robust CD8 T Cell immunity. One possible basis for this may be the relationship of Dendritic Cell (DC) Subset topography to micro-anatomically dictated antigen dispersal and subsequent down-stream innate and adaptive Cellular engagement. To address this issue directly in situ we utilized advanced quantitative imaging approaches (histo-cytometry) and found that protein immunization led to non-linear concentration gradients across draining lymph nodes. This graded distribution in turn affected which DC Subset had access to high vs. low concentrations of antigen. Because DC Subsets are specialized in MHC-I vs. MHC-II antigen processing and presentation, the result of this intersection of antigen dispersal and Cell positioning was the predominant residence of MHC-I presenting DC in regions with lower antigen bioavailability. Modulating the antigen dose directly influenced the fraction of MHC-I presenting DC with access to sufficient antigen to activate T Cells, allowing for direct control over the clonal diversity and magnitude of the response. These findings indicate that tissue microanatomy related to DC Subset distribution and antigen dissemination within the lymph node is a critical regulator of CD8 T Cell immunity. This research was supported by the Intramural Research Program of the NIH, NIAID.
-
histo cytometry a method for highly multiplex quantitative tissue imaging analysis applied to Dendritic Cell Subset microanatomy in lymph nodes
Immunity, 2012Co-Authors: Michael Y Gerner, Wolfgang Kastenmuller, Ina Ifrim, Juraj Kabat, Ronald N. GermainAbstract:Summary Flow cytometry allows highly quantitative analysis of complex dissociated populations at the cost of neglecting their tissue localization. In contrast, conventional microscopy methods provide spatial information, but visualization and quantification of Cellular Subsets defined by complex phenotypic marker combinations is challenging. Here, we describe an analytical microscopy method, "histo-cytometry," for visualizing and quantifying phenotypically complex Cell populations directly in tissue sections. This technology is based on multiplexed antibody staining, tiled high-resolution confocal microscopy, voxel gating, volumetric Cell rendering, and quantitative analysis. We have tested this technology on various innate and adaptive immune populations in murine lymph nodes (LNs) and were able to identify complex Cellular Subsets and phenotypes, achieving quantitatively similar results to flow cytometry, while also gathering Cellular positional information. Here, we employ histo-cytometry to describe the spatial segregation of resident and migratory Dendritic Cell Subsets into specialized microanatomical domains, suggesting an unexpected LN demarcation into discrete functional compartments.