Blockade of allergic airway inflammation following systemic treatment with a B7-dendritic cell (PD-L2) cross-linking human antibody.
We present a novel immunotherapeutic strategy using a human B7-DC cross-linking Ab that prevents lung inflammation, airway obstruction, and hyperreactivity to allergen in a mouse model of allergic inflammatory airway disease. Dendritic cells (DC) have the ability to skew the immune response toward a Th1 or Th2 polarity. The sHIgM12 Ab functions in vitro by cross-linking the costimulatory family molecule B7-DC (PD-L2) on DC up-regulating IL-12 production, homing to lymph nodes, and T cell-activating potential of these APCs. Using chicken OVA as a model Ag, the administration of sHIgM12 Ab to BALB/c mice blocked lung inflammation, airway pathology, and responsiveness to methacholine, even after animals were presensitized and a Th2-polarized immune response was established. This therapeutic strategy was ineffective in STAT4-deficient animals, indicating that IL-12 production is critical in this system. Moreover, the polarity of the immune response upon in vitro restimulation with Ag is changed in wild-type mice, with a resulting decrease in Th2 cytokines IL-4 and IL-5 and an increase in the immunoregulatory cytokine IL-10. These studies demonstrate that the immune response of hypersensitized responders can be modulated using B7-DC cross-linking Abs, preventing allergic airway disease upon re-exposure to allergen.
Radhakrishnan
Suresh
S
Department of Immunology, and Division of Allergic Disease and Internal Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Iijima
Koji
K
Kobayashi
Takao
T
Rodriguez
Moses
M
Kita
Hirohito
H
Pease
Larry R
LR
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000276:immunology*; D016207:Cytokines / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D008168:Lung / Q000473:pathology; D051379:Mice; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012137:Respiratory System / Q000276:immunology*; D013154:Spleen / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000906:Antibodies; D018122:B7-1 Antigen; D016207:Cytokines; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein