Dendritic cells activated by cross-linking B7-DC (PD-L2) block inflammatory airway disease

Suresh Radhakrishnan, Koji Iijima, Takao Kobayashi, Hirohito Kita, Larry R Pease

Research output: Contribution to journalArticle

29 Citations (Scopus)

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-α, IFN-γ, and IL-10. In contrast, IL-4 was not produced by cells isolated from animals receiving B7-DC XAb. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)668-674
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume116
Issue number3
DOIs
StatePublished - Sep 2005

Fingerprint

Dendritic Cells
Ovalbumin
Lung Diseases
Antibodies
Adoptive Transfer
Antigens
Interleukin-4
Interleukin-10
Spleen
Asthma
Lymph Nodes
Lymphocytes
Lung

Keywords

  • Antibody
  • Asthma
  • B7-DC
  • Dendritic cells
  • Immunotherapy
  • Inflammatory lung disease
  • PD-L2
  • T1
  • T2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Dendritic cells activated by cross-linking B7-DC (PD-L2) block inflammatory airway disease. / Radhakrishnan, Suresh; Iijima, Koji; Kobayashi, Takao; Kita, Hirohito; Pease, Larry R.

In: Journal of Allergy and Clinical Immunology, Vol. 116, No. 3, 09.2005, p. 668-674.

Research output: Contribution to journalArticle

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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-α, IFN-γ, and IL-10. In contrast, IL-4 was not produced by cells isolated from animals receiving B7-DC XAb. Conclusion: 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.",
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