Abstract:
:The most common reason for heart failure in young adults is dilated cardiomyopathy often resulting from myocarditis. Clinical studies and animal models provide evidence that an autoimmune response against heart myosin is the underlying reason for the disease. IL-12 has been suggested to play a key role in development of experimental autoimmune myocarditis (EAM), as IL-12p40 and IL-12Rbeta1 knockouts are protected from disease. In this study, we have compared IL-12p40-/- mice, IL-12p35-/- mice and mice treated with a neutralizing IL-23 antibody in EAM and found that in fact IL-23, not IL-12, is responsible for inflammatory heart disease. However, these cytokines appear to have redundant activity for priming and expansion of autoreactive CD4 T cells, as specific T cell proliferation was only defective in the absence of both cytokines. IL-23 has been suggested to promote a pathogenic IL-17-producing T cell population. We targeted IL-17 by capitalizing on an active vaccination approach that effectively breaks B cell tolerance. Neutralization of IL-17 reduced myocarditis and heart autoantibody responses, suggesting that IL-17 is the critical effector cytokine responsible for EAM. Thus, targeting of IL-23 and IL-17 by passive and active vaccination strategies holds promise as a therapeutic approach to treat patients at risk for development of dilated cardiomyopathy.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Sonderegger I,Röhn TA,Kurrer MO,Iezzi G,Zou Y,Kastelein RA,Bachmann MF,Kopf Mdoi
10.1002/eji.200636484subject
Has Abstractpub_date
2006-11-01 00:00:00pages
2849-56issue
11eissn
0014-2980issn
1521-4141journal_volume
36pub_type
杂志文章abstract::Biochemical and functional studies have demonstrated major histocompatibility complex (MHC) class II-restricted presentation of peptides derived from cytosolic proteins, but the underlying processing and presentation pathways have remained elusive. Here we show that endogenous presentation of an epitope derived from t...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200323730
更新日期:2003-05-01 00:00:00
abstract::Human ILCs are classically categorized into five subsets; cytotoxic CD127- CD94+ NK cells and non-cytotoxic CD127+ CD94- , ILC1s, ILC2s, ILC3s, and LTi cells. Here, we identify a previously unrecognized subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ I...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.202048696
更新日期:2020-12-09 00:00:00
abstract::Secretion of proinflammatory mediators by activated macrophages plays an important role in the immune response to Trypanosoma cruzi. We have previously reported that AgC10, a glycosylphosphatidylinositol-anchored mucin from T. cruzi, inhibits TNF secretion by activated macrophages (de Diego, J., Punzon, C., Duarte, M....
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200324660
更新日期:2004-06-01 00:00:00
abstract::The class II transactivator (CIITA) has been referred to as the "master control factor" for the expression of MHC class II (MHCII) genes. As our knowledge on the specificity and function of CIITA grows, it is becoming increasingly evident that this sobriquet is entirely justified. First, despite extensive investigatio...
journal_title:European journal of immunology
pub_type: 杂志文章,评审
doi:10.1002/eji.200424964
更新日期:2004-06-01 00:00:00
abstract::Physical exercise, mental stress, or infusion of beta-adrenergic agonists result in an increase in the number of natural killer (NK) cells in the peripheral circulation. In view of the specific migration pattern of NK cells in vivo, it has been suggested that these cells may be released from the marginating pool in bl...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830231230
更新日期:1993-12-01 00:00:00
abstract::The major histocompatibility complex (MHC)-encoded transporter associated with antigen processing (TAP) delivers cytosolic peptides to the lumen of the endoplasmic reticulum (ER) for presentation by MHC class I molecules. For the rat, it has been demonstrated that TAP polymorphism results in the selection of different...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830250808
更新日期:1995-08-01 00:00:00
abstract::CD4+ alpha beta T cell populations that develop in mice deficient in MHC class II (through 'knockout' of either the Aalpha, or the Abeta chain of the I-A(b) molecule) comprise a major 'single-positive' (SP) CD4+ CD8- subset (60-90%) and a minor 'double-positive' (DP) CD4+ CD8alpha beta+ subset (10-40%). Many DP T cell...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200324463
更新日期:2004-03-01 00:00:00
abstract::To study the question when and where self peptides become associated with major histocompatibility complex class II molecules for tolerance induction, we recently developed a system in which the intracellular site(s) of antigen expression could be manipulated using gene cloning techniques. We previously constructed a ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830210613
更新日期:1991-06-01 00:00:00
abstract::In humans and in BALB/c mice, immune responses to the hormone insulin use evolutionarily related VHV (human) and VHIX (murine) gene families. To determine if these structural relationships include regulatory elements, BALB/c mice were pretreated with autologous immunoglobulin G (IgG) monoclonal antibodies (mAb) that r...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830220938
更新日期:1992-09-01 00:00:00
abstract::Cytotoxic T lymphocytes (CTL) recognize antigenic peptides presented by major histocompatibility complex class I (MHC-I) molecules on the surface of target cells. Optimal induction of CD8+ CTL depends on the amount of relevant peptide/MHC-I complexes and the presence of co-stimulatory molecules on antigen-presenting c...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830241118
更新日期:1994-11-01 00:00:00
abstract::Anti-CD3 mAb can modulate graft rejection and attenuate autoimmune diseases but their mechanism(s) of action remain unclear. CD8(+) T cells with regulatory function are induced in vitro by Teplizumab, a humanized anti-CD3 antibody and inhibit responses of autologous and allogeneic T cells. They inhibit CD4(+) T-cell p...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201040485
更新日期:2010-10-01 00:00:00
abstract::The germ-line V gene segments encoding the subgroups A and G of the BALB/c V kappa 21 family were cloned and assigned to the previously described 30-kb cluster of the V kappa 21 family. Sequence comparison revealed close homology between the two gene segments at the DNA and the predicted amino acid sequence level, ind...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830191031
更新日期:1989-10-01 00:00:00
abstract::Interleukin (IL)-4-transgenic mice were used as a model system to study the consequences of low levels of IL-4 expression for the expression of other cytokines examined by quantitative polymerase chain reaction (PCR). For this purpose, a plasmid was constructed which contains, in tandem array, 5' and 3' primer sequenc...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830220511
更新日期:1992-05-01 00:00:00
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
更新日期:1989-12-01 00:00:00
abstract::The functional role of the T8 antigen of human T cells was studied by inhibition with anti-T8 monoclonal antibodies (mAb) of the cytotoxic action of T8+ cytotoxic T lymphocyte clones (CTL). All clones were allospecific and directed against HLA-B7. The ability of seven different anti-T8 mAb to inhibit the cytotoxicity ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830161109
更新日期:1986-11-01 00:00:00
abstract::Despite the differences in the molecular structure between lipopolysaccharides (LPS) isolated from Escherichia coli, Klebsiella pneumoniae or Salmonella typhimurium, the potential differences in their biological effects in vivo have not been investigated. In the present study, TNF and LT double knock-out (TNF-/-LT-/-)...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200109)31:9<2529::aid-immu25
更新日期:2001-09-01 00:00:00
abstract::The contribution of the costimulatory molecules B7-1 and B7-2 to the in vivo differentiation of Th cells remains controversial. The infection of resistant and susceptible strains of mice with the parasite Leishmania major provides a well-established model for studying in vivo differentiation of CD4+ T cells. We have i...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200206)32:6<1764::AID-IMMU1764>3
更新日期:2002-06-01 00:00:00
abstract::T helper cell type 2 (Th2) cells when triggered by antibodies to CD3 acquire the capacity to stimulate the polyclonal proliferation of syngeneic, resting B cells. Here, we tested the ability of various monoclonal antibodies (mAb) to block the B cell proliferation-inducing potential of such activated Th2 cells. We demo...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830220246
更新日期:1992-02-01 00:00:00
abstract::We recently reported that differentiation of CD8(+) T cells from the naïve to the effector state involves the upregulation of glucose-dependent metabolism. Glucose deprivation or inhibition of glycolysis by 2-deoxy-D-glucose (2-DG) selectively inhibited production of IFN-gamma but not of IL-2. To determine a more glob...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200838289
更新日期:2008-09-01 00:00:00
abstract::The adoptive transfer of CD4(+)CD25(+) natural regulatory T cells (Treg) is a promising strategy for the treatment of autoimmune diseases and the prevention of alloresponses after transplantation. Clinical trials exploring this strategy require efficient in vitro expansion of this rare cell population. Protocols devel...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200838904
更新日期:2009-04-01 00:00:00
abstract::Leishmaniases are a major international public health problem, and macrophages are crucial for host resistance to this parasite. To determine if phosphatase and tensin homologue deleted on chromosome ten (Pten), a negative regulator of the PI3K pathway, plays a role in macrophage-mediated resistance to Leishmania, we ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200737302
更新日期:2008-05-01 00:00:00
abstract::Cells in homeostasis metabolize glucose mainly through the tricarboxylic acid cycle and oxidative phosphorylation, while activated cells switch their basal metabolism to aerobic glycolysis. In this study, we examined whether metabolic reprogramming toward aerobic glycolysis is important for the host response to Mycoba...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201546259
更新日期:2016-11-01 00:00:00
abstract::Terminal differentiation of B cells into antibody-secreting cells is the foundation of humoral immune response. B-1 cells, which are different from B-2 cells, preferentially differentiate into plasma cells. CMTM7 is a MARVEL-domain-containing membrane protein predominantly expressed in B cells that plays an important ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201948363
更新日期:2020-06-01 00:00:00
abstract::The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested that this is partially due to activation of plasmacytoid dendritic cells (pDCs), the main producers of interferon (IFN)-α...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201646725
更新日期:2017-02-01 00:00:00
abstract::The TCR structure of T cell hybridomas recognizing a tumor glycan-defined epitope has been studied using reverse transcriptase-PCR and gene sequencing. The hybridomas had been raised against a glycopeptide, T72(Tn), consisting of the mouse hemoglobin-derived decapeptide Hb(67 - 76), O-glycoslated in position 72 with a...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199909)29:09<2759::AID-IMM
更新日期:1999-09-01 00:00:00
abstract::A T3 complex-bearing subpopulation was characterized within an in vivo cycling T4-8- early thymocyte compartment which contains cells constitutively expressing interleukin 2 and transferrin receptors. We show differentiation in vitro of both mature subsets of thymocytes (T3+4+8- and T3+4-8+) from the above T4-8- compa...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830160611
更新日期:1986-06-01 00:00:00
abstract::The presentation of islet antigens in the pancreatic LNs (PLNs) of mice is a developmentally regulated process. It has been hypothesized that, during physiological tissue remodeling, a wave of neonatal β-cell apoptosis may initiate diabetes in autoimmune-prone strains of mice. If true, increasing or decreasing physiol...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201141476
更新日期:2011-08-01 00:00:00
abstract::Twenty-seven B cell hybridomas derived from spleen cells of nonimmunized, 6-day-old BALB/c mice and previously characterized serologically were screened for VH-gene expression: hybridomas expressing the two most D-proximal VH-gene families, 7183 and QUPC 52 were over-represented in this sample. Strikingly, clones sero...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830170315
更新日期:1987-03-01 00:00:00
abstract::This Viewpoint series provides authoritative and detailed outlines of exciting areas of DC research. Some of the subjects that frequently come up include development of DC; distribution of DC in lymphoid and non-lymphoid tissues such as skin, intestine and lung; different forms or subsets of DC; and the role of DC in ...
journal_title:European journal of immunology
pub_type:
doi:10.1002/eji.201040733
更新日期:2010-08-01 00:00:00
abstract::It has been reported that Thy-1+CD3+CD4-CD8- cells as well as Langerhans cells migrate from organ-cultured murine skin into culture medium. We examined whether these Thy-1+ populations of migrating cells were derived from Thy-1+ dendritic epidermal T cells (Thy-1+ DEC) and found that they were Thy-1+CD3+CD4-CD8-gamma/...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830230746
更新日期:1993-07-01 00:00:00