I2CT

@article{flacher_skin_2012,

title = {Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ Ŧ cell responses},

author = {V Flacher and C H Tripp and B Haid and A Kissenpfennig and B Malissen and P Stoitzner and J Idoyaga and N Romani},

year  = {2012},

date = {2012-03-01},

journal = {Journal of Immunology},

volume = {188},

number = {1550-6606 (Electronic)},

pages = {2146--2155},

abstract = {Incorporation of Ags by dendritic cells (DCs) increases when Ags are targeted to endocytic receptors by mAbs. We have previously demonstrated in the mouse that mAbs against C-type lectins administered intradermally are taken up by epidermal Langerhans cells (LCs), dermal Langerin(neg) DCs, and dermal Langerin(+) DCs in situ. However, the relative contribution of these skin DC subsets to the induction of immune responses after Ag targeting has not been addressed in vivo. We show in this study that murine epidermal LCs and dermal DCs transport intradermally injected mAbs against the lectin receptor DEC-205/CD205 in vivo. Skin DCs targeted in situ with mAbs migrated through lymphatic vessels in steady state and inflammation. In the skin-draining lymph nodes, targeting mAbs were found in resident CD8alpha(+) DCs and in migrating skin DCs. More than 70% of targeted DCs expressed Langerin, including dermal Langerin(+) DCs and LCs. Numbers of targeted skin DCs in the nodes increased 2-3-fold when skin was topically inflamed by the TLR7 agonist imiquimod. Complete removal of the site where OVA-coupled anti-DEC-205 had been injected decreased endogenous cytotoxic responses against OVA peptide-loaded target cells by 40-50%. Surprisingly, selective ablation of all Langerin(+) skin DCs in Langerin-DTR knock-in mice did not affect such responses independently of the adjuvant chosen. Thus, in cutaneous immunization strategies where Ag is targeted to DCs, Langerin(+) skin DCs play a major role in transport of anti-DEC-205 mAb, although Langerin(neg) dermal DCs and CD8alpha(+) DCs are sufficient to subsequent CD8(+) T cell responses},

keywords = {administration & dosage, Animals, Antibodies, antibody, Antigen, Antigens, Biosynthesis, C-Type, C-type lectin, CD, Cell Surface, Comparative Study, Cytotoxic, Dendritic Cells, DERMATOLOGY, Gene Knock-In Techniques, Genetics, imiquimod, immune response, IMMUNE-RESPONSES, Immunization, Immunology, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, inflammation, Inflammation Mediators, Injections, Intradermal, knock-in, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, LYMPHATIC VESSEL, Lymphatic Vessels, mAb, Mannose-Binding Lectins, MEDIATOR, metabolism, Mice, Minor Histocompatibility Antigens, mouse, murine, Organ Culture Techniques, Ovum, pathology, physiology, Protein, Protein Transport, Rats, Receptor, Receptors, RESPONSES, Skin, SUBSETS, Surface, T-Lymphocytes, target, Team-Mueller, TLR7, transgenic},

pubstate = {published},

tppubtype = {article}

}

@article{romani_targeting_2012,

title = {Targeting skin dendritic cells to improve intradermal vaccination},

author = {N Romani and V Flacher and C H Tripp and F Sparber and S Ebner and P Stoitzner},

doi = {10.1007/82_2010_118},

issn = {0070-217X},

year  = {2012},

date = {2012-01-01},

journal = {Current Topics in Microbiology and Immunology},

volume = {351},

pages = {113--138},

abstract = {Vaccinations in medicine are typically administered into the muscle beneath the skin or into the subcutaneous fat. As a consequence, the vaccine is immunologically processed by antigen-presenting cells of the skin or the muscle. Recent evidence suggests that the clinically seldom used intradermal route is effective and possibly even superior to the conventional subcutaneous or intramuscular route. Several types of professional antigen-presenting cells inhabit the healthy skin. Epidermal Langerhans cells (CD207/langerin(+)), dermal langerin(neg), and dermal langerin(+) dendritic cells (DC) have been described, the latter subset so far only in mouse skin. In human skin langerin(neg) dermal DC can be further classified based on their reciprocal expression of CD1a and CD14. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Yet, specializations of these different populations have become apparent. Langerhans cells in human skin appear to be specialized for induction of cytotoxic T lymphocytes; human CD14(+) dermal DC can promote antibody production by B cells. It is currently attempted to rationally devise and improve vaccines by harnessing such specific properties of skin DC. This could be achieved by specifically targeting functionally diverse skin DC subsets. We discuss here advances in our knowledge on the immunological properties of skin DC and strategies to significantly improve the outcome of vaccinations by applying this knowledge.},

keywords = {Adaptive Immunity, administration & dosage, Analysis, Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, B CELLS, B-Lymphocytes, Bacterial Infections, Biosynthesis, C-Type, CD, CD14, CD1a, Cell Lineage, cytokine, Cytokines, cytology, Cytotoxic, Dendritic Cells, DERMATOLOGY, DERMIS, Drug Delivery Systems, Expression, Human, Humans, Immunity, Immunology, INDUCTION, Injections, Innate, Intradermal, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Lymphocytes, Mannose-Binding Lectins, methods, Mice, mouse, Muscle, prevention & control, PRODUCTION, Protein, review, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines, Virus Diseases},

pubstate = {published},

tppubtype = {article}

}

@article{flacher_epidermal_2010,

title = {Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis},

author = {Vincent Flacher and Christoph H Tripp and Patrizia Stoitzner and Bernhard Haid and Susanne Ebner and Barbara Del Frari and Franz Koch and Chae Gyu Park and Ralph M Steinman and Juliana Idoyaga and Nikolaus Romani},

doi = {10.1038/jid.2009.343},

issn = {1523-1747},

year  = {2010},

date = {2010-03-01},

journal = {The Journal of Investigative Dermatology},

volume = {130},

number = {3},

pages = {755--762},

abstract = {Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin- CD103- mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions.},

keywords = {Animals, Antibodies, antibody, Antigen, Antigen Presentation, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, BASEMENT MEMBRANE, C-Type, C-type lectin, CD103, CD8+ T cells, Cell Division, Cell Movement, Cells, Culture, Cultured, cytology, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermal Cells, Epidermis, function, Human, Humans, Immunology, in situ, IN VITRO, In vivo, Inbred BALB C, Inbred C57BL, Injections, Intradermal, Langerhans Cells, LECTIN, Lectins, mAb, Mannose-Binding Lectins, Membrane, Mice, Monoclonal, mouse, murine, Pharmacology, Proliferation, Protein, Receptor, Skin, Surface, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Vaccination, vaccine, Vaccines},

pubstate = {published},

tppubtype = {article}

}

@article{lacerda_tissue_2008,

title = {Tissue histology and physiology following intravenous administration of different types of functionalized multiwalled carbon nanotubes},

author = {Lara Lacerda and Hanene Ali-Boucetta and Maria A Herrero and Giorgia Pastorin and Alberto Bianco and Maurizio Prato and Kostas Kostarelos},

doi = {10.2217/17435889.3.2.149},

issn = {1748-6963},

year  = {2008},

date = {2008-04-01},

journal = {Nanomedicine (London, England)},

volume = {3},

number = {2},

pages = {149--161},

abstract = {BACKGROUND: Carbon nanotubes (CNTs) constitute one of the most important types of nanomaterials, increasingly gaining interest as tools for nanomedicine applications, such as sensors, implants or delivery systems. Our groups have reported previously that chemical functionalization of CNTs can lead to their almost complete elimination from the body of animals through the urinary excretion route. The administration of CNTs may, however, impact the physiological function of organs through which CNTs traverse or accumulate. AIM: The present study addresses the short-term impact (first 24 h) of intravenous administration of various types of multiwalled nanotubes (MWNTs) on the physiology of healthy mice. MATERIALS & METHODS: Nonfunctionalized, purified MWNTs (pMWNTs) and different types of water-dispersible, functionalized MWNTs (f-MWNTs) were tail-vein injected. Histological examination of tissues (kidney, liver, spleen and lung) harvested 24 h post-administration indicated that organ accumulation depended on the degree of ammonium (NH(3)(+)) functionalization at the f-MWNT surface. RESULTS: The higher the degree of functionalization of MWNT-NH(3)(+), the less their accumulation in tissues. pMWNTs coated with autologous serum proteins prior to injection accumulated almost entirely in the lung and liver in large dark clusters. Moreover, various indicators of serum and urine analyses also confirmed that MWNT-NH(3)(+) injections did not induce any physiological abnormality in all major organs within the first 24 h post-injection. Interestingly, no abnormalities were observed either for f-MWNTs highly functionalized with carboxylate groups (diethylentriaminepentaacetic-functionalized MWNTs) or by upscaling to the highest doses ever injected so far in vivo (20 mg/kg). CONCLUSION: The high degree of f-MWNT functionalization responsible for adequate individualization of nanotubes and not the nature of the functional groups was the critical factor leading to less tissue accumulation and normal tissue physiology at least within the first 24 h post-administration, even at the highest carbon nanotube doses ever administered in any study today.},

keywords = {Animals, carbon, Female, I2CT, Inbred BALB C, Injections, Intravenous, Mice, Nanotubes, Organ Specificity, Team-Bianco, Tissue Distribution},

pubstate = {published},

tppubtype = {article}

}

@article{singh_tissue_2006,

title = {Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers},

author = {Ravi Singh and Davide Pantarotto and Lara Lacerda and Giorgia Pastorin and Cédric Klumpp and Maurizio Prato and Alberto Bianco and Kostas Kostarelos},

doi = {10.1073/pnas.0509009103},

issn = {0027-8424},

year  = {2006},

date = {2006-02-01},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

volume = {103},

number = {9},

pages = {3357--3362},

abstract = {Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, single-walled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium ((111)In) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h) of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications.},

keywords = {Animals, carbon, Electron, Female, Half-Life, I2CT, Inbred BALB C, Indium Radioisotopes, Injections, Intravenous, Mice, Microscopy, Molecular Structure, Nanotubes, Pentetic Acid, Team-Bianco, Tissue Distribution, Transmission},

pubstate = {published},

tppubtype = {article}

}

@article{van_mierlo_activation_2004,

title = {Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication},

author = {Geertje J D van Mierlo and Zita F H M Boonman and Hélène M H Dumortier and Annemieke Th den Boer and Marieke F Fransen and Jan Nouta and Ellen I H van der Voort and Rienk Offringa and René E M Toes and Cornelis J M Melief},

doi = {10.4049/jimmunol.173.11.6753},

issn = {0022-1767},

year  = {2004},

date = {2004-12-01},

journal = {Journal of Immunology (Baltimore, Md.: 1950)},

volume = {173},

number = {11},

pages = {6753--6759},

abstract = {The fate of naive CD8(+) T cells is determined by the environment in which they encounter MHC class I presented peptide Ags. The manner in which tumor Ags are presented is a longstanding matter of debate. Ag presentation might be mediated by tumor cells in tumor draining lymph nodes or via cross-presentation by professional APC. Either pathway is insufficient to elicit protective antitumor immunity. We now demonstrate using a syngeneic mouse tumor model, expressing an Ag derived from the early region 1A of human adenovirus type 5, that the inadequate nature of the antitumor CTL response is not due to direct Ag presentation by the tumor cells, but results from presentation of tumor-derived Ag by nonactivated CD11c(+) APC. Although this event results in division of naive CTL in tumor draining lymph nodes, it does not establish a productive immune response. Treatment of tumor-bearing mice with dendritic cell-stimulating agonistic anti-CD40 mAb resulted in systemic efflux of CTL with robust effector function capable to eradicate established tumors. For efficacy of anti-CD40 treatment, CD40 ligation of host APC is required because adoptive transfer of CD40-proficient tumor-specific TCR transgenic CTL into CD40-deficient tumor-bearing mice did not lead to productive antitumor immunity after CD40 triggering in vivo. CpG and detoxified LPS (MPL) acted similarly as agonistic anti-CD40 mAb with respect to CD8(+) CTL efflux and tumor eradication. Together these results indicate that dendritic cells, depending on their activation state, orchestrate the outcome of CTL-mediated immunity against tumors, leading either to an ineffective immune response or potent antitumor immunity.},

keywords = {Adenovirus E1A Proteins, Animals, Antibodies, Antigen-Presenting Cells, Antigens, CD11c Antigen, CD40 Antigens, Cross-Priming, Cultured, Cytotoxic, Cytotoxicity, Dendritic Cells, Dumortier, Epitopes, Experimental, I2CT, Immunologic, Inbred C57BL, Injections, Intralesional, Intravenous, Knockout, Male, Mice, Monoclonal, Neoplasms, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic, tumor, Tumor Cells, Viral},

pubstate = {published},

tppubtype = {article}

}

@article{dumortier_b_2000,

title = {B and Ŧ cell responses to the spliceosomal heterogeneous nuclear ribonucleoproteins A2 and B1 in normal and lupus mice},

author = {H Dumortier and F Monneaux and B Jahn-Schmid and J P Briand and K Skriner and P L Cohen and J S Smolen and G Steiner and S Muller},

doi = {10.4049/jimmunol.165.4.2297},

issn = {0022-1767},

year  = {2000},

date = {2000-08-01},

journal = {Journal of Immunology (Baltimore, Md.: 1950)},

volume = {165},

number = {4},

pages = {2297--2305},

abstract = {Autoantibodies directed against spliceosomal heterogeneous nuclear ribonucleoproteins (hnRNPs) are a typical feature of rheumatoid arthritis, systemic lupus erythematosus, and mixed-connective tissue disease. With the aim of investigating a potential pathogenic role of these Abs, we have studied the Ab response to A2/B1 hnRNPs in different murine models of lupus. The specificity of anti-A2/B1 Abs was tested with a series of 14 overlapping synthetic peptides covering the region 1-206 of A2 that contains most of the epitopes recognized by patients' Abs. A major epitope recognized very early during the course of the disease by Abs from most of MRL lpr/lpr mice but not from other lupus mice and from mice of different MHC haplotypes immunized against B1 was identified in residues 50-70. This peptide contains a highly conserved sequence RGFGFVTF also present in other hnRNPs and small nuclear ribonucleoproteins. Abs reacting with a second A2 epitope identified in residues 35-55 were detectable several weeks later, suggesting an intramolecular B cell epitope spreading during the course of the disease. We identified several T cell epitopes within the region 35-175 that generated an effective Th cell response with IL-2 and IFN-gamma secretion in nonautoimmune CBA/J mice sharing the same MHC haplotype H-2k as MRL/lpr mice. None of the peptides stimulated T cells primed in vivo with B1. Because Abs to peptide 50-70 were detected significantly earlier than Abs reacting with other A2 peptides and the protein itself, it is possible that within the protein, this segment contains residues playing an initiator role in the induction of the anti-A2/B1 and antispliceosome Ab response.},

keywords = {Amino Acid Sequence, Animals, Autoantibodies, B-Lymphocytes, Dumortier, Epitope Mapping, Female, Heterogeneous Nuclear, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Humans, I2CT, Immunoglobulin G, Inbred BALB C, Inbred C57BL, Inbred CBA, Inbred MRL lpr, Injections, Lupus Nephritis, Lymphocyte Activation, Male, Mice, Molecular Sequence Data, Monneaux, Peptide Fragments, Recombinant Proteins, Ribonucleoproteins, RNA, Spliceosomes, Subcutaneous, T-Lymphocytes, Team-Dumortier, transgenic},

pubstate = {published},

tppubtype = {article}

}

@article{meziere_vivo_1997,

title = {In vivo Ŧ helper cell response to retro-inverso peptidomimetics},

author = {C Mézière and M Viguier and H Dumortier and R Lo-Man and C Leclerc and J G Guillet and J P Briand and S Muller},

issn = {0022-1767},

year  = {1997},

date = {1997-10-01},

journal = {Journal of Immunology (Baltimore, Md.: 1950)},

volume = {159},

number = {7},

pages = {3230--3237},

abstract = {Peptide analogues containing reversed peptide bonds between each residue along the peptide sequence (retro-inverso modification) have been analyzed for their antigenic and in vivo immunogenic properties in the MHC II and Th cell response context. Two antigenic peptides were selected for this study, namely peptide 103-115 of poliovirus VP1, which is involved in the production of Abs that neutralize the infectivity of the virus, and peptide 435-446 from the third constant region of mouse heavy chain IgG2a allopeptide gamma 2ab, which mimics a corneal Ag implicated in autoimmune keratitis. In a competition assay performed in vitro using reference hybridomas of known MHC class II restriction, both retro-inverso analogues bound (although more weakly in our test) to I-Ad and/or I-Ed class II molecules. However, in both cases, this lower affinity was apparently largely compensated in vivo, as a T cell response (with IL-2 secretion), equivalent to that obtained with the wild-type peptides, was observed following immunization of BALB/c mice with the retro-inverso analogues. Moreover, these T cells proliferated and produced IL-2 in response to the cognate peptides. It is concluded that the T cell receptors of T cells primed in vivo with the retro-inverso analogues readily cross-react with parent and retro-inverso analogue-MHC complexes. The approach of using pseudopeptides containing changes involving the backbone, and not the orientation of side chains, may thus be promising to design potent immunogens for class II-restricted T cells.},

keywords = {Amino Acid Sequence, Animals, Antibodies, Antigen, Capsid, Capsid Proteins, Dumortier, Female, Helper-Inducer, Histocompatibility Antigens Class II, I2CT, Immunoglobulin Allotypes, Immunoglobulin G, Inbred BALB C, Injections, Intraperitoneal, Lymphocyte Activation, Mice, Molecular Sequence Data, Peptide Fragments, Poliovirus, Protein Binding, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier, Viral},

pubstate = {published},

tppubtype = {article}

}

@article{feyereisen_dynamics_1976,

title = {Dynamics of ecdysone metabolism after ingestion and injection in Locusta migratoria},

author = {R Feyereisen and Marie Lagueux and Jules A Hoffmann},

issn = {0016-6480},

year  = {1976},

date = {1976-07-01},

journal = {Gen. Comp. Endocrinol.},

volume = {29},

number = {3},

pages = {319--327},

keywords = {Animals, Ecdysone, Grasshoppers, hoffmann, Hydroxylation, Injections, Intestines, Larva, M3i, Malpighian Tubules, Oral},

pubstate = {published},

tppubtype = {article}

}

@article{hoffmann_prothoracic_1974,

title = {Prothoracic glands in the regulation of ecdysone titres and metabolic fate of injected labelled ecdysone in Locusta migratoria},

author = {Jules A Hoffmann and J Koolman},

issn = {0022-1910},

year  = {1974},

date = {1974-08-01},

journal = {J. Insect Physiol.},

volume = {20},

number = {8},

pages = {1593--1601},

keywords = {Animals, Ecdysone, Grasshoppers, hoffmann, Injections, M3i},

pubstate = {published},

tppubtype = {article}

}