title: Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses.
abstract: Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas humoral responses to most antigens require further collaboration between primed, antigen-specific helper T cells and naive or memory B cells. To determine whether antigens delivered to DCs in lymphoid organs induce T cell help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), to DCs in the presence of a maturation stimulus and assayed for antibodies to a hapten, (4-hydroxy-3-nitrophenyl) acetyl (NP), after boosting with OVA-NP. A single DC-targeted immunization elicited long-lived T cell helper responses to the carrier protein, leading to large numbers of antibody-secreting cells and high titers of high-affinity antihapten immunoglobulin Gs. Small doses of DC-targeted OVA induced higher titers and a broader spectrum of anti-NP antibody isotypes than large doses of OVA in alum adjuvant. Similar results were obtained when the circumsporozoite protein of Plasmodium yoelii was delivered to DCs. We conclude that antigen targeting to DCs combined with a maturation stimulus produces broad-based and long-lived T cell help for humoral immune responses.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Silvia B
authors.initials: SB
authors.lastname: Boscardin
authors.forename: Julius C R
authors.initials: JC
authors.lastname: Hafalla
authors.forename: Revati F
authors.initials: RF
authors.lastname: Masilamani
authors.forename: Alice O
authors.initials: AO
authors.lastname: Kamphorst
authors.forename: Henry A
authors.initials: HA
authors.lastname: Zebroski
authors.forename: Urvashi
authors.initials: U
authors.lastname: Rai
authors.forename: Alexandre
authors.initials: A
authors.lastname: Morrot
authors.forename: Fidel
authors.initials: F
authors.lastname: Zavala
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Nussenzweig
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002645:Chickens; D003713:Dendritic Cells / Q000276:immunology*; D006241:Haptens / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010967:Plasmodium yoelii / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D006241:Haptens; D007074:Immunoglobulin G; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; C041524:aluminum sulfate; D010047:Ovalbumin