B7-H3 Contributes to the Development of Pathogenic Th2 Cells in a Murine Model of Asthma

J Immunol. 2008 Sep 15;181(6):4062-71. doi: 10.4049/jimmunol.181.6.4062.

Abstract

B7-H3 is a new member of the B7 family. The receptor for B7-H3 has not been identified, but it seems to be expressed on activated T cells. Initial studies have shown that B7-H3 provides a stimulatory signal to T cells. However, recent studies suggest a negative regulatory role for B7-H3 in T cell responses. Thus, the immunological function of B7-H3 is controversial and unclear. In this study, we investigated the effects of neutralizing anti-B7-H3 mAb in a mouse model of allergic asthma to determine whether B7-H3 contributes to the development of pathogenic Th2 cells and pulmonary inflammation. Administration of anti-B7-H3 mAb significantly reduced airway hyperreactivity with a concomitant decrease in eosinophils in the lung as compared with control IgG-treated mice. Treatment with anti-B7-H3 mAb also resulted in decreased production of Th2 cytokines (IL-4, IL-5, and IL-13) in the draining lymph node cells. Although blockade of B7-H3 during the induction phase abrogated the development of asthmatic responses, B7-H3 blockade during the effector phase did not inhibit asthmatic responses. These results indicated an important role for B7-H3 in the development of pathogenic Th2 cells during the induction phase in a murine model of asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / administration & dosage
  • Allergens / immunology
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Asthma / immunology*
  • Asthma / metabolism
  • Asthma / pathology
  • Asthma / prevention & control
  • B7 Antigens
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology
  • B7-1 Antigen / physiology
  • Cell Differentiation / immunology*
  • Cell Line, Tumor
  • Cell Movement / immunology
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Lung / immunology
  • Lung / pathology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Th2 Cells / pathology*

Substances

  • Allergens
  • Antibodies, Monoclonal
  • B7 Antigens
  • B7-1 Antigen
  • Cd276 protein, mouse
  • Ovalbumin