Abstract
Although exogeneous "danger" signals such as LPS can activate APC to produce a Th1 response, the nature of events initiating a Th2 response is controversial. We now show that pathogen-derived products have the capacity to induce bone marrow-derived dendritic cell cultures to acquire a phenotype that promotes the differentiation of naive CD4+ T cells toward either a Th1 or Th2 phenotype. Thus, LPS-matured dendritic cells (DC1) promote a Th1 response (increased generation of IFN-gamma and reduced production of IL-4) by Ag-stimulated CD4+ T cells from the DO.11.10 transgenic mouse expressing a TCR specific for an OVA peptide (OVA323-339). In contrast, a phosphorylcholine-containing glycoprotein, ES-62, secreted by the filarial nematode, Acanthocheilonema viteae, which generates a Th2 Ab response in vivo, is found to induce the maturation of dendritic cells (DC2) with the capacity to induce Th2 responses (increased IL-4 and decreased IFN-gamma). In addition, we show that the switch to either Th1 or Th2 responses is not effected by differential regulation through CD80 or CD86 and that a Th2 response is achieved in the presence of IL-12.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / physiology
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Antigens, Differentiation, T-Lymphocyte / biosynthesis
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Antigens, Differentiation, T-Lymphocyte / physiology
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B7-1 Antigen / physiology
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B7-2 Antigen
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Cell Differentiation / immunology
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dipetalonema / immunology*
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Dipetalonema / physiology
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Helminth Proteins / administration & dosage
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Helminth Proteins / immunology*
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Helminth Proteins / metabolism*
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Helminth Proteins / physiology
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Immunoglobulin G / biosynthesis
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Immunophenotyping
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Injections, Subcutaneous
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Interleukin-10 / physiology
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Interleukin-12 / physiology
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Lipopolysaccharides / pharmacology
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Signal Transduction / immunology*
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T-Lymphocytes, Helper-Inducer / immunology
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Th2 Cells / cytology
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Th2 Cells / immunology*
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Th2 Cells / metabolism
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Th2 Cells / parasitology
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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B7-1 Antigen
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B7-2 Antigen
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Cd86 protein, mouse
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Helminth Proteins
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Immunoglobulin G
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Lipopolysaccharides
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Membrane Glycoproteins
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Interleukin-10
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Interleukin-12