title: Directed antigen targeting in vivo identifies a role for CD103+ dendritic cells in both tolerogenic and immunogenic T-cell responses.
abstract: The αE integrin chain CD103 identifies a subset of migratory dendritic cells (DCs) in the gut, lung, and skin. To gain further understanding of the function of CD103(+) DCs in regulating adaptive immunity in vivo, we coupled ovalbumin (OVA) to the CD103 antibody M290 (M290.OVA). Intraperitoneal injection of M290.OVA induced OVA-specific CD8(+) and CD4(+) T-cell proliferation in lymph nodes (LNs) of wild-type but not CD103(-/-) mice, or in mice depleted of CD11c(+) cells. In the absence of maturation stimuli, systemic antigen targeting to CD103(+) DCs led to tolerance of CD8(+) T cells, whereas coadministration of adjuvant induced cytotoxic T-lymphocyte (CTL) immunity and antibody production. Mucosal intratracheal application of M290.OVA also induced T-cell proliferation in mediastinal LNs, yet the functional outcome was tolerance that inhibited subsequent development of allergic airway inflammation and immunoglobulin E (IgE) responses to inhaled OVA. These findings identify antigen targeting to CD103(+) DCs as a potential strategy to regulate immune responses in nonlymphoid mucosal tissues.
authors.affiliation: Immunology Section, Lund University, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Semmrich
authors.forename: M
authors.initials: M
authors.lastname: Plantinga
authors.forename: M
authors.initials: M
authors.lastname: Svensson-Frej
authors.forename: H
authors.initials: H
authors.lastname: Uronen-Hansson
authors.forename: T
authors.initials: T
authors.lastname: Gustafsson
authors.forename: A M
authors.initials: AM
authors.lastname: Mowat
authors.forename: U
authors.initials: U
authors.lastname: Yrlid
authors.forename: B N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: W W
authors.initials: WW
authors.lastname: Agace
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000917:Antibody Formation; D000941:Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004333:Drug Administration Routes; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D056747:Immunomodulation; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D015703:Antigens, CD; D039001:Integrin alpha Chains; D011993:Recombinant Fusion Proteins; C091367:alpha E integrins; D010047:Ovalbumin