title: Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo.
abstract: Increasing evidence suggests that antibodies can have stimulatory effects on T-cell immunity. However, the contribution of circulating antigen-specific antibodies on MHC class I cross-priming in vivo has not been conclusively established. Here, we defined the role of circulating antibodies in cross-presentation of antigen to CD8(+)  T cells. Mice with hapten-specific circulating antibodies, but naϊve for the T-cell antigen, were infused with haptenated antigen and CD8(+)  T-cell induction was measured. Mice with circulating hapten-specific antibodies showed significantly enhanced cross-presentation of the injected antigen compared with mice that lacked these antibodies. The enhanced cross-presentation in mice with circulating antigen-specific antibodies was associated with improved antigen capture by APCs. Importantly, CD11c(+)  APCs were responsible for the enhanced and sustained cross-presentation, although CD11c(-)  APCs had initially captured a significant amount of the injected antigen. Thus, in vivo formation of antigen-antibody immune complexes improves MHC class I cross-presentation, and CD8(+)  T-cell activation, demonstrating that humoral immunity can aid the initiation of systemic cellular immunity. These findings have important implications for the understanding of the action of therapeutic antibodies against tumor-associated antigens intensively used in the clinic nowadays.
authors.affiliation: Department of Immunohematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nadine
authors.initials: N
authors.lastname: van Montfoort
authors.forename: Sara M
authors.initials: SM
authors.lastname: Mangsbo
authors.forename: Marcel G M
authors.initials: MG
authors.lastname: Camps
authors.forename: Wendy W C
authors.initials: WW
authors.lastname: van Maren
authors.forename: Ingrid E C
authors.initials: IE
authors.lastname: Verhaart
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.forename: Jan Wouter
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.forename: Ferry
authors.initials: F
authors.lastname: Ossendorp
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D006241:Haptens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D039521:CD11c Antigen; D006241:Haptens; D015395:Histocompatibility Antigens Class I; D012710:Serum Albumin, Bovine; D010047:Ovalbumin