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Some of the Early Events Underlying Th2. Cell Maturation and Susceptibility to Leishmania major Infection in BALB/c Mice
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H. Himmelrich
Veröffentlicht/Copyright:
1. Juni 2005
Abstract
The first experimental evidence for the development of polarized CD4+ Th1 and Th2 responses in vivo has been obtained using the murine model of infection with Leishmania major, an intracellular parasite of macrophages in their vertebrate host. Genetically determined resistance and susceptibility to infection with this parasite have been clearly demonstrated to result from the development of polarized Th1 and Th2 responses, respectively. Using this model system, the dominant role of cytokines in the induction of polarized CD4+ responses has been validated in vivo. The requisite role of IL-4 in mediating both Th2 differentiation and susceptibility to infection in BALB/c mice has directed interest towards the search for evidence of IL-4 production early after infection and identification of its cellular source. We have been able to demonstrate a burst of IL-4 production in susceptible BALB/c mice within the first day of infection with L. major and could establish that this rapidly produced IL-4 instructed Th2 lineage commitment of subsequently activated CD4+ T cells and stabilized this commitment by downregulating IL-12 Rβ2 chain expression, resulting in susceptibility to infection. Strikingly, this early IL-4 response to infection resulted from the cognate recognition of a single epitope in a distinctive antigen, LACK, from this complex microorganism by a restricted population of CD4+ T cells that express Vβ4-Vα8 T cell receptors.
:
Published Online: 2005-06-01
Published in Print: 1999-07-01
Copyright © 1999 by Walter de Gruyter GmbH & Co. KG
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Artikel in diesem Heft
- Paul Nurse Felix Hoppe-Seyler Lecturer 1999
- Cyclin Dependent Kinases and Regulation of the Fission Yeast Cell Cycle
- Paper of the Year 1998
- Autonomous Regulation in Mammalian Mitochondrial DNA Transcription
- Prospects for the Precise Engineering of Plant Genomes by Homologous Recombination
- The Glycosphingolipidoses from Disease to Basic Principles of Metabolism
- The Dual Role of Lipopolysaccharide as Effector and Target Molecule
- A Unified Mechanism of Enzymatic Synthesis of Two Calcium Messengers: Cyclic ADP-Ribose and NAADP
- The Tranquilizing Injection of Yersinia Proteins: A Pathogens Strategy to Resist Host Defense
- IL-6 Type Cytokine Receptor Complexes: Hexamer, Tetramer or Both?
- Genetically Engineered and Synthetic Allergen Derivatives: Candidates for Vaccination against Type I Allergy
- Molecular Farming of Recombinant Antibodies in Plants
- Chimeric Restriction Enzymes: What Is Next?
- Viroids with Hammerhead Ribozymes: Some Unique Structural and Functional Aspects with Respect to Other Members of the Group
- Mutagenesis via Insertional or Restriction Enzyme-Mediated Integration (REMI) as a Tool to Tag Pathogenicity Related Genes in Plant Pathogenic Fungi
- Role of Mitochondria in Parkinson Disease
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- Mutant p53: Gain-of-Function Oncoproteins and Wild-Type p53 Inactivators
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- Mutations of Calcium Channel beta Subunit Genes in Mice
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- Some of the Early Events Underlying Th2. Cell Maturation and Susceptibility to Leishmania major Infection in BALB/c Mice
- Universal and Unique Features of Kinesin Motors: Insights from a Comparison of Fungal and Animal Conventional Kinesins
- Elementary Steps in Protein Folding
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- The Two SH2-Domain-Containing Inositol 5-Phosphatases SHIP1 and SHIP2 Are Coexpressed in Human T Lymphocytes
- Differential Distribution of Four Hyperpolarization-Activated Cation Channels in Mouse Brain
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