A filarial nematode-secreted product signals dendritic cells to acquire a phenotype that drives development of Th2 cells.
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.
Whelan
M
M
The Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom.
Harnett
M M
MM
Houston
K M
KM
Patel
V
V
Harnett
W
W
Rigley
K P
KP
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004153:Dipetalonema / Q000276:immunology* / Q000502:physiology; D015801:Helminth Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D007074:Immunoglobulin G / Q000096:biosynthesis; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D015801:Helminth Proteins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D018664:Interleukin-12