title: CD8alpha(-) and CD8alpha(+) subclasses of dendritic cells undergo phenotypic and functional maturation in vitro and in vivo.
abstract: Dendritic cells (DCs) are essential for the priming of immune responses. This antigen-presenting function of DCs develops in sequence in a process called maturation, during which they become potent sensitizers of naïve T cells but reduce their ability to capture and process antigens. Some heterogeneity exists in mouse-DC populations, and two distinct subsets of DCs expressing high levels of CD11c can be identified on the basis of CD8alpha expression. We have studied the phenotype and maturation state of mouse splenic CD8alpha(-) and CD8alpha(+) DCs. Both subsets were found to reside in the spleen as immature cells and to undergo a phenotypic maturation upon culture in vitro in GM-CSF-containing medium or in vivo in response to lipopolysaccharide. In vitro and in vivo analyses showed that this maturation process is an absolute requisite for DCs to acquire their T-cell priming capacity, transforming CD8alpha(-) and CD8alpha(+) DCs into potent and equally efficient activators of naïve CD4(+) and CD8(+) T cells. Furthermore, these results highlight the importance that environmental factors may have on the ability of DC subsets to influence Th responses qualitatively; i.e., the ability to drive Th1 versus Th2 differentiation may not be fixed immutably for each DC subset.
authors.affiliation: Department of Discovery Research, Immunex Corporation, Seattle, Washington, USA. desmedtt@immunex.com
authors.forename: T
authors.initials: T
authors.lastname: De Smedt
authors.forename: E
authors.initials: E
authors.lastname: Butz
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: R
authors.initials: R
authors.lastname: Maldonado-López
authors.forename: B
authors.initials: B
authors.lastname: Pajak
authors.forename: M
authors.initials: M
authors.lastname: Moser
authors.forename: C
authors.initials: C
authors.lastname: Maliszewski
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology* / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen / Q000032:analysis; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D016827:CD8 Antigens; C431698:CD8alpha antigen; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D011994:Recombinant Proteins; C084881:flt3 ligand protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin