title: Dendritic cells activated by cross-linking B7-DC (PD-L2) block inflammatory airway disease.
abstract: BACKGROUND
  Allergic asthma is an increasing clinical problem that might be addressed with immunologically based interventions. A novel human antibody that activates human and mouse dendritic cells (DCs) by cross-linking B7-DC has strong immunomodulatory properties and blocks antigen-induced inflammatory lung disease in mice.
  
  
  OBJECTIVE
  We sought to evaluate the ability of activated DCs to mediate an antibody-induced protective response against inflammatory lung disease.
  
  
  METHODS
  An adoptive transfer strategy was used to test the ability of antibody treatments to activate DCs, inducing a protective response against inflammatory lung disease in mice presensitized to ovalbumin (OVA). After transfer of activated DCs, recipient mice were exposed repeatedly to airway antigen and evaluated for changes in immune reactivity and airway inflammatory disease.
  
  
  RESULTS
  Animals presensitized to OVA receiving either systemic treatments with B7-DC cross-linking antibody (XAb) or adoptively transferred antibody-activated DCs were completely protected from airway inflammatory responses normally induced by repeated exposure to OVA. Lymphocytes isolated from spleens or lung-draining lymph nodes of treated animals were highly responsive to OVA and secreted TNF-alpha, IFN-gamma, and IL-10. In contrast, IL-4 was not produced by cells isolated from animals receiving B7-DC XAb.
  
  
  CONCLUSIONS
  Activation of DCs with B7-DC XAb ex vivo before adoptive transfer into presensitized mice is sufficient to protect animals completely from inflammatory lung disease induced by subsequent repeated airway exposure to the offending antigen. This finding is consistent with our hypothesis that in vivo administration of B7-DC XAb modulates the immune response by activating endogenous DCs.
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Radhakrishnan
authors.forename: Koji
authors.initials: K
authors.lastname: Iijima
authors.forename: Takao
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kita
authors.forename: Larry R
authors.initials: LR
authors.lastname: Pease
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018122:B7-1 Antigen / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007075:Immunoglobulin M / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D061027:Programmed Cell Death 1 Ligand 2 Protein; D013154:Spleen / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D016207:Cytokines; D007075:Immunoglobulin M; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein