title: Role of interleukin-23-dependent antifungal immune responses in dendritic cell-vaccinated mice.
abstract: CD40 ligand (CD40L) transduction of antigen-pulsed dendritic cells (DCs) can result in antigen-specific humoral immune responses even in CD4(+) T-cell-depleted settings. Here, we show that CD40L transduction of DCs results in the induction of interleukin-12p40 (IL-12p40), IL-12p70, and IL-23. Using DCs that were deficient in IL-12p40, IL-12p35, or IL-23p19, we show that these molecules are dispensable for primary IgG1 responses to Pneumocystis, but IgG2c was dependent on IL-12p40 and IL-23p19 but not IL-12p35. Antigen-specific recall responses in CD4-deficient mice were critically dependent on IL-12p40 and IL-23p19 expression in DCs and were not affected by the lack of IL-12p35. To confirm that this defect in recall was due to IL-23, transduction of IL-12p40(-/-) DCs with a recombinant adenovirus expressing functional IL-23 restored recall responses in DC-vaccinated CD4-deficient mice. These data show that DC-produced IL-23 is critical for vaccine-induced antigen-specific IgG2c and recall antibody responses in the setting of CD4(+) T-cell depletion.
authors: LSU Health Sciences Center, Department of Genetics, CSRB 657, 533 Bolivar St., New Orleans, LA 70112, USA.
authors: Mingquan
authors: M
authors: Zheng
authors: Rekha R
authors: RR
authors: Rapaka
authors: Amy C
authors: AC
authors: Yu
authors: Judd E
authors: JE
authors: Shellito
authors: Jay K
authors: JK
authors: Kolls
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D053765:Interleukin-12 Subunit p35 / Q000172:deficiency / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology* / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000172:deficiency / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011010:Pneumocystis / Q000276:immunology*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic; D014611:Vaccination
chemical_list: D015704:CD4 Antigens; C406563:IgG2c receptor; D007074:Immunoglobulin G; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D017452:Receptors, IgG; D023201:CD40 Ligand