Coupling of antigen to cholera toxin for dendritic cell vaccination promotes the induction of MHC class I-restricted cytotoxic T cells and the rejection of a cognate antigen-expressing model tumor.

Abstract:

:We previously demonstrated that cholera toxin (CT) is highly efficient as a combined carrier and adjuvant for dendritic cell (DC) vaccination, inducing strong Th1-dominated B cell and CD4(+) T cell responses. In this study we show that vaccination with DC pre-pulsed ex vivo with CT-conjugated OVA (OVA-CT) gives rise to OVA-specific CD8(+) T cells that produce IFN-gamma and are cytotoxic for OVA-expressing E.G7 tumor cells both in vitro and in vivo. The induction of specific CD8(+) CTL by OVA-CT-treated DC was associated with enhanced presentation of OVA peptide (SIINFEKL) on MHC class I in combination with an overall activation of the pulsed DC. Vaccination of mice with OVA-CT-pulsed DC resulted in rejection of already established MHC class I-positive, MHC class II-negative, OVA-expressing E.G7 tumors in an antigen-specific, CD8(+) T cell-dependent fashion and was associated with high numbers of tumor-infiltrating CD8(+) T cells. Conjugation of antigen to CT facilitated DC uptake of the linked antigen through the GM1 receptor-binding B subunit and induced strong activation-maturation signals through the biologically active A subunit. These results have interesting implications for DC vaccination aimed at inducing CTL immune responses.

journal_name

Eur J Immunol

authors

Eriksson K,Sun JB,Nordström I,Fredriksson M,Lindblad M,Li BL,Holmgren J

doi

10.1002/eji.200324368

keywords:

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

1272-81

issue

5

eissn

0014-2980

issn

1521-4141

journal_volume

34

pub_type

杂志文章
  • Induction of strong hepatitis B virus (HBV) specific T helper cell and cytotoxic T lymphocyte responses by therapeutic vaccination in the trimera mouse model of chronic HBV infection.

    abstract::Humanized BALB/c mice (termed trimera mice) conditioned by lethal total body irradiation and bone marrow transplantation from SCID mice have been described to support rapid engraftment of human peripheral blood mononuclear cells (PBMC) and the induction of strong B and T cell responses after immunization in vivo. More...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200107)31:7<2071::aid-immu2071>3

    authors: Böcher WO,Dekel B,Schwerin W,Geissler M,Hoffmann S,Rohwer A,Arditti F,Cooper A,Bernhard H,Berrebi A,Rose-John S,Shaul Y,Galle PR,Löhr HF,Reisner Y

    更新日期:2001-07-01 00:00:00

  • Inhibition of clonal expansion by Foxp3 expression as a mechanism of controlled T-cell responses and autoimmune disease.

    abstract::The essential role of the transcription factor Foxp3 in the development and function of Treg has been well documented. The role of Foxp3 in non-Treg, however, is not fully understood. Emerging evidence indicates that Foxp3 expression is not confined to CD4+CD25+ Treg. The present study shows that in Foxp3 transgenic (...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200939404

    authors: Guo L,Tian J,Marinova E,Zheng B,Han S

    更新日期:2010-01-01 00:00:00

  • Antibody-dependent cellular cytotoxicity against tumor cells. II. The promonocyte identified as effector cell.

    abstract::Macrophage precursor cells were cultured from the bone marrow of mice in a liquid culture system in the presence of conditioned medium. To separate their different maturation stages, they were passed through a discontinuous Ficoll density gradient, treated with iron plus magnet or passed through glass bead columns. Th...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830090404

    authors: Domzig W,Lohmann-Matthes ML

    更新日期:1979-04-01 00:00:00

  • Epstein Barr virus infection and immune defense related to HLA-DR15: consequences for multiple sclerosis.

    abstract::MS is a multifactorial disease in which a series of genetic and non-genetic, environmental factors plays a role in its etiology. In particular, HLA class II alleles, mainly HLADRB1*15:01 (HLA-DR15), increase the risk for this disease. Out of several environmental factors, and with regard to infections, EBV remains to ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.202049030

    authors: Olsson T

    更新日期:2020-12-22 00:00:00

  • Differential effects of the tryptophan metabolite 3-hydroxyanthranilic acid on the proliferation of human CD8+ T cells induced by TCR triggering or homeostatic cytokines.

    abstract::Production of indoleamine 2,3-dioxygenase (IDO) by tumor cells, leading to tryptophan depletion and production of immunosuppressive metabolites, may facilitate immune tolerance of cancer. IDO gene is also expressed in dendritic cells (DC) upon maturation induced by lipopolysaccarides or IFN. We investigated IDO gene e...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200535616

    authors: Weber WP,Feder-Mengus C,Chiarugi A,Rosenthal R,Reschner A,Schumacher R,Zajac P,Misteli H,Frey DM,Oertli D,Heberer M,Spagnoli GC

    更新日期:2006-02-01 00:00:00

  • Existence of a small population of IL-2R beta hi TCRint cells in SCG and MRL-lpr/lpr mice which produce normal Fas mRNA and Fas molecules from the lpr gene.

    abstract::Mice carrying the lpr gene, SCG and MRL-lpr/lpr mice, were used to characterize the phenotype and lpr gene of abnormally proliferating T cells in these mice. A major population which expanded in these mice were T cells expressing intermediate (int) levels of T cell receptor (TCR) (and CD3) and the phenotype of interle...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830260702

    authors: Yamagiwa S,Kuwano Y,Hasegawa K,Sato K,Ohtsuka K,Iiai T,Tomiyama K,Watanabe H,Sugahara S,Seki S,Asakura H,Abo T

    更新日期:1996-07-01 00:00:00

  • Depletion of NK cells results in disseminating lethal infection with Bordetella pertussis associated with a reduction of antigen-specific Th1 and enhancement of Th2, but not Tr1 cells.

    abstract::IFN-gamma plays a critical role in protection against Bordetella pertussis, but Th1 cells are only detectable after the infection has started to resolve, suggesting a protective role for innate IFN-gamma early in infection. Here, we demonstrate significant recruitment of NK cells and NKT cells into the lungs following...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200425092

    authors: Byrne P,McGuirk P,Todryk S,Mills KH

    更新日期:2004-09-01 00:00:00

  • Site-directed mutagenesis of the chemokine receptor CXCR6 suggests a novel paradigm for interactions with the ligand CXCL16.

    abstract::Chemokine receptor CXCR6 mediates the chemotaxis and adhesion of leukocytes to soluble and membrane-anchored forms of CXCL16, and is an HIV-1 co-receptor. Here, we describe the effects of mutation of acidic extracellular CXCR6 residues on receptor function. Although most CXCR6 mutants examined were expressed at levels...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200838269

    authors: Petit SJ,Chayen NE,Pease JE

    更新日期:2008-08-01 00:00:00

  • Mitochondrial reactive oxygen species suppress humoral immune response through reduction of CD19 expression in B cells in mice.

    abstract::Reactive oxygen species (ROS) are implicated in the modulation of diverse processes including immune responses. To evaluate the effects of metabolic ROS produced by mitochondria on B-cell function and development, we created transgenic (Tg) mice expressing a phosphorylation-defective mutant of succinate dehydrogenase ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201646342

    authors: Ogura M,Inoue T,Yamaki J,Homma MK,Kurosaki T,Homma Y

    更新日期:2017-02-01 00:00:00

  • NK cell-extrinsic IL-18 signaling is required for efficient NK-cell activation by vaccinia virus.

    abstract::NK cells are important for the control of vaccinia virus (VV) in vivo. Recent studies have shown that multiple pathways are required for effective activation of NK cells. These include both TLR-dependent and -independent pathways, as well as the NKG2D activating receptor that recognizes host stress-induced NKG2D ligan...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201344134

    authors: Brandstadter JD,Huang X,Yang Y

    更新日期:2014-09-01 00:00:00

  • Granzyme A expression by normal rat natural killer (NK) cells in vivo and by interleukin 2-activated NK cells in vitro.

    abstract::Granzyme A (TSP-1) is a serine esterase expressed in cytotoxic T and natural killer (NK) cell lines. Its presence in in vivo primed T cells is disputed at present. Here we show that normal rat NK cells contain granzyme A in vivo and that its expression is augmented by their short-term in vitro treatment with IL 2. Gra...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830190328

    authors: Velotti F,Palmieri G,Morrone S,Piccoli M,Frati L,Santoni A

    更新日期:1989-03-01 00:00:00

  • Serologic distinction between the rabbit kappa L chain allotype b4 and an allele b4.

    abstract::Rabbit kappa light (L) chain allotypes are controlled by the allelic genes b4, b5, b6, b9 and a recently described allele b4v. The product of the b4v gene differs from that of b4 by at least two amino acid substitutions in the constant region. A serologic distinction between the b4 and b4v allotyes has now been detect...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830090107

    authors: Smith LJ,Sogh JA,Kindt TJ,Mandy WJ

    更新日期:1979-01-01 00:00:00

  • A combination of stem cell factor and granulocyte colony-stimulating factor enhances the growth of human progenitor B cells supported by murine stromal cell line MS-5.

    abstract::We have developed a long-term culture system using the murine bone marrow stromal cells MS-5 to support the growth of progenitor B cells with CD34-, CD10+, CD19+, and cytoplasmic mu chain (C mu)-negative surface phenotype from human CD34+ cells purified from umbilical cord blood (CB). When 10(3) CD34+ cells/well were ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199803)28:03<855::AID-IMMU

    authors: Nishihara M,Wada Y,Ogami K,Ebihara Y,Ishii T,Tsuji K,Ueno H,Asano S,Nakahata T,Maekawa T

    更新日期:1998-03-01 00:00:00

  • In vivo role of IFN-gamma produced by antigen-presenting cells in early host defense against intracellular pathogens.

    abstract::Antigen-presenting cells (APC), including dendritic cells and macrophages, produce a large amount of interferon (IFN)-gamma, a crucial cytokine for the control of infectious diseases. To elucidate the role of IFN-gamma from APC in vivo, we employed cytokine receptor common gamma subunit (gamma c) and recombination-act...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200323292

    authors: Suzue K,Asai T,Takeuchi T,Koyasu S

    更新日期:2003-10-01 00:00:00

  • TGF-beta1 enhances SDF-1alpha-induced chemotaxis and homing of naive T cells by up-regulating CXCR4 expression and downstream cytoskeletal effector molecules.

    abstract::The migration of immunocytes within the extracellular matrix (ECM) is influenced by the activation state of the incoming cell and its responses to the presence of chemokines and cytokines. We studied the regulatory role of TGF-beta1 on T cell homing to secondary lymphatic organs, such as the spleen, and chemotaxis wit...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200201)32:1<193::AID-IMMU193>3.0

    authors: Franitza S,Kollet O,Brill A,Vaday GG,Petit I,Lapidot T,Alon R,Lider O

    更新日期:2002-01-01 00:00:00

  • Identification of a new epitope of the 4F2/44D7 molecular complex present on sarcolemma and isolated cardiac fibers.

    abstract::The murine monoclonal antibody (mAb) CB43, raised against the K-562 erythroleukemia line, reacts with monocytes, tissue macrophages, thymocytes and with all the human lines tested but not with resting lymphocytes, large granular lymphocytes, granulocytes and erythrocytes. However, activated lymphocytes and natural kil...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830190102

    authors: Bellone G,Alloatti G,Levi R,Geuna M,Tetta C,Peruzzi L,Letarte M,Malavasi F

    更新日期:1989-01-01 00:00:00

  • Polymorphisms and haplotypes in the human immunoglobulin kappa locus.

    abstract::By comparing the restriction patterns of the DNA from 23 unrelated individuals 16 polymorphisms were defined which allowed us to differentiate between the duplicated copies Op, Ap, Lp and Od, Ad, Ld of the kappa locus (p for the C kappa proximal, d for the distal copy). Some of these duplication-differentiating polymo...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830210808

    authors: Pargent W,Schäble KF,Zachau HG

    更新日期:1991-08-01 00:00:00

  • Lymphocyte specificity to protein antigens. III. Capacity of low responder mice to beef cytochrome c to respond to a peptide fragment of the molecule.

    abstract::Lymph node cells derived from A.TH or A.TL mice primed with beef cytochrome c show striking patterns of reactivity when assayed in vitro for antigen-induced T cell proliferation. Whereas cells from A.TH mice respond specifically to beef cytochrome c or peptides composed of amino acids 1-65 and 81-104, cells from A.TL ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830110210

    authors: Corradin G,Chiller JM

    更新日期:1981-02-01 00:00:00

  • Leptin: nourishment for the immune system.

    abstract::Leptin, a protein produced by adipocytes, exerts several functions, including modulation of the immune response. A report in this issue of the European Journal of Immunology describes for the first time the effect of either leptin receptor deficiency or blockade on murine dendritic cell (DC) maturation, survival and f...

    journal_title:European journal of immunology

    pub_type: 杂志文章,评审

    doi:10.1002/eji.200636770

    authors: Fantuzzi G

    更新日期:2006-12-01 00:00:00

  • MHC-peptide-specific antibodies reveal inefficient presentation of an HLA-A*0201-restricted, Melan-A-derived peptide after active intracellular processing.

    abstract::MHC-peptide-specific Fab antibodies binding to HLA-A*0201 complexes presenting the wild-type EAAGIGILTV (EAA) or analogue Melan-A 10-mer ELAGIGILTV (ELA) peptide were generated to study efficacy of peptide processing and presentation. None of the selected Fab antibodies detected the naturally processed EAA/HLA-A*0201 ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200636545

    authors: Held G,Wadle A,Dauth N,Stewart-Jones G,Sturm C,Thiel M,Zwick C,Dieckmann D,Schuler G,Hoogenboom HR,Lévy F,Cerundolo V,Pfreundschuh M,Renner C

    更新日期:2007-07-01 00:00:00

  • Memory phenotype CD8(+) T cells in IL-15 transgenic mice are involved in early protection against a primary infection with Listeria monocytogenes.

    abstract::We recently constructed IL-15 transgenic (Tg) mice using cDNA encoding a secretable isoform of the IL-15 precursor protein under the control of an MHC class I promoter. The IL-15 Tg mice exhibited resistance against a primary infection with Listeria monocytogenes. The numbers of memory CD8(+) T cells were markedly inc...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200103)31:3<757::aid-immu757>3.0

    authors: Yajima T,Nishimura H,Ishimitsu R,Yamamura K,Watase T,Busch DH,Pamer EG,Kuwano H,Yoshikai Y

    更新日期:2001-03-01 00:00:00

  • Characterization of CD4+ T cells in mouse bone marrow. I. Increased activated/memory phenotype and altered TCR Vbeta repertoire.

    abstract::A significant proportion of memory B cells home to bone marrow (BM) which is a major site of anamnestic antibody responses in mice. We hypothesized that memory T cells likewise accumulate in BM perhaps to provide help for antibody production, and that the compartment of CD4+ T cells in BM of unimmunized mice would be ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199903)29:03<1051::AID-IMM

    authors: Price PW,Cerny J

    更新日期:1999-03-01 00:00:00

  • Acute infection with the intestinal parasite Trichuris muris has long-term consequences on mucosal mast cell homeostasis and epithelial integrity.

    abstract::A hallmark of parasite infection is the accumulation of innate immune cells, notably granulocytes and mast cells, at the site of infection. While this is typically viewed as a transient response, with the tissue returning to steady state once the infection is cleared, we found that mast cells accumulated in the large-...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201646738

    authors: Sorobetea D,Holm JB,Henningsson H,Kristiansen K,Svensson-Frej M

    更新日期:2017-02-01 00:00:00

  • Transendothelial chemotaxis of human alpha/beta and gamma/delta T lymphocytes to chemokines.

    abstract::Two subpopulations of human T lymphocytes expressing different antigen receptors, alpha/beta and gamma/delta, emigrate into inflamed tissues in distinctive patterns. We compared the transmigration of alpha/beta and gamma/delta T cells to C-C and C-X-C chemokines using an in vitro transendothelial chemotaxis assay. The...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199801)28:01<104::AID-IMMU

    authors: Roth SJ,Diacovo TG,Brenner MB,Rosat JP,Buccola J,Morita CT,Springer TA

    更新日期:1998-01-01 00:00:00

  • Identification of a novel subpopulation of germinal center B cells characterized by expression of IgD and CD70.

    abstract::CD27, which belongs to the tumor necrosis factor receptor family, is expressed on germinal center (GC) but not on naive B cells, suggesting an important function of this molecule in the regulation of the GC reaction. We described here the expression of CD70, which is the ligand for CD27. We observed that in most tonsi...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830260508

    authors: Lens SM,Keehnen RM,van Oers MH,van Lier RA,Pals ST,Koopman G

    更新日期:1996-05-01 00:00:00

  • Dendritic cell-derived IL-15 controls the induction of CD8 T cell immune responses.

    abstract::The development and the differentiation of CD8(+) T cells are dependent on IL-15. Here, we have studied the source and mechanism of how IL-15 modulates CD8(+) T cell-mediated Th1 immune responses by employing two delayed-type hypersensitivity (DTH) models. IL-15-deficient (IL-15(-/-)) mice or mice treated with soluble...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200324545

    authors: Rückert R,Brandt K,Bulanova E,Mirghomizadeh F,Paus R,Bulfone-Paus S

    更新日期:2003-12-01 00:00:00

  • DTR-mediated conditional cell ablation-Progress and challenges.

    abstract::Cell ablation is a valuable complement to mutagenesis for experimentally defining specific cell functions in physiology and pathophysiology in small animal models. One of the most popular ablation strategies involves transgenic expression of a primate diphtheria toxin receptor (DTR) on murine cells that are otherwise ...

    journal_title:European journal of immunology

    pub_type: 评论,杂志文章

    doi:10.1002/eji.201847527

    authors: Ruedl C,Jung S

    更新日期:2018-07-01 00:00:00

  • Comprehensive analysis of HIV Gag-specific IFN-gamma response in HIV-1- and HIV-2-infected asymptomatic patients from a clinical cohort in The Gambia.

    abstract::Majority of HIV-2-infected individuals meet the criteria of long-term non-progressors. This has been linked to superior qualitative HIV-2-specific cellular immune responses that correlate with viral control. However, it is unknown whether this is due to frequent targeting of immunodominant Gag epitopes in HIV-2 than H...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200838759

    authors: Ondondo BO,Rowland-Jones SL,Dorrell L,Peterson K,Cotten M,Whittle H,Jaye A

    更新日期:2008-12-01 00:00:00

  • Subsets of thymopoietic rat thymocytes defined by expression of the CD2 antigen and the MRC OX-22 determinant of the leukocyte-common antigen CD45.

    abstract::The MRC OX-22 monoclonal antibody recognizes a restricted determinant of the rat leukocyte-common antigen (L-CA, CD45), which is expressed on most peripheral T cells and all B cells. In contrast only 2%-3% of thymocytes are OX-22+ and these are now shown to be mostly of the immature CD4-CD8- (double-negative, DN), phe...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830191217

    authors: Law DA,Spruyt LL,Paterson DJ,Williams AF

    更新日期:1989-12-01 00:00:00

  • Deficiency of high-affinity anti-beta-D-galactosidase antibodies in selected low immune responder mice.

    abstract::Amount and affinity of anti-beta-D-galactosidase-activating antibodies (AAb) were studied in two lines of mice obtained by selective breeding for antibody response to heterologous erythrocytes. These lines, referred to as high (H) and low (L) lines, differ also in their responses to many antigens. Concerning AAb amoun...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830090312

    authors: Conway de Macario E,Heumann AM,Macario AJ,Biozzi G

    更新日期:1979-03-01 00:00:00