Murine CTLA4-IgG treatment inhibits airway eosinophilia and hyperresponsiveness and attenuates IgE upregulation in a murine model of allergic asthma

Am J Respir Cell Mol Biol. 1997 Sep;17(3):386-92. doi: 10.1165/ajrcmb.17.3.2679.


Antigen-specific T-cell activation requires the engagement of the T-cell receptor (TCR) with antigen as well as the engagement of appropriate costimulatory molecules. One of the most important pathways of costimulation is the interaction of CD28 on the T cell with B7-1/B7-2 on antigen-presenting cells. In the present study, we have examined the in vivo effects of blocking the CD28:B7 T-cell costimulatory pathway by administration of mCTLA4-IgG in a murine model of allergic asthma. Mice were sensitized with ovalbumin and exposed to repeated ovalbumin inhalation challenges. In mice treated with a control antibody at the time of ovalbumin challenge a significant increase in the number of eosinophils (12.8 +/- 4.3 x 10(3) cells, P < 0.05) in the bronchoalveolar lavage (BAL) fluid and airway hyperresponsiveness to methacholine (49 +/- 15%, P < 0.05) was observed. In addition, serum levels of ovalbumin-specific IgE were significantly (P < 0.01) increased after ovalbumin challenge compared with saline challenge (1,133 +/- 261 experimental units [EU]/ml and 220 +/- 63 EU/ml, respectively). In mice treated with mCTLA4-IgG at the time of ovalbumin challenge, the infiltration of eosinophils into BAL fluid and the development of airway hyperresponsiveness to methacholine were completely inhibited. The upregulation of ovalbumin-specific IgE levels in serum was attenuated by mCTLA4-IgG treatment. Furthermore, addition of mCTLA4-IgG to cultures of parabronchial lymph node cells from sensitized mice inhibited the ovalbumin-induced interleukin-4 production. These data indicate the therapeutic potential of blocking T-lymphocyte costimulation by CTLA4-IgG as a possible immunosuppressive treatment for patients with allergic asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Administration, Inhalation
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / metabolism
  • Antigens, Differentiation / pharmacology*
  • Asthma / immunology*
  • Bronchi / cytology
  • Bronchi / drug effects
  • Bronchi / immunology
  • Bronchial Hyperreactivity / prevention & control*
  • Bronchoconstrictor Agents / pharmacology
  • CTLA-4 Antigen
  • Cytokines / biosynthesis
  • Disease Models, Animal
  • Eosinophilia / immunology*
  • Immunoconjugates*
  • Immunoglobulin E / physiology*
  • Immunoglobulin G / metabolism
  • Immunoglobulin G / pharmacology*
  • Immunosuppressive Agents / metabolism
  • Immunosuppressive Agents / pharmacology*
  • Male
  • Methacholine Chloride / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Ovalbumin / pharmacology
  • Protein Binding / immunology
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / immunology
  • Specific Pathogen-Free Organisms
  • Spleen / cytology
  • Up-Regulation


  • Antigens, CD
  • Antigens, Differentiation
  • Bronchoconstrictor Agents
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Cytokines
  • Immunoconjugates
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Methacholine Chloride
  • Immunoglobulin E
  • Abatacept
  • Ovalbumin