Journal article
CD28 Interactions with Either CD80 or CD86 Are Sufficient to Induce Allergic Airway Inflammation in Mice
American journal of respiratory cell and molecular biology, Vol.21(4), pp.498-509
10/01/1999
DOI: 10.1165/ajrcmb.21.4.3714
PMID: 10502560
Abstract
Previous studies have shown that the pan CD28/cytotoxic T lymphocyte antigen (CTL)A-4 antagonist CTLA4 immunoglobulin (Ig) inhibits eosinophilic airway inflammation in Schistosoma mansoni–sensitized and airway-challenged mice. In the present study, the importance of CD28 as well as the individual roles of CD80 and CD86 were examined in this system using wild-type and CD28 knockout (KO) mice. Unlike wild-type controls, CD28KO mice did not produce systemic IgE or eosinophilic airway inflammation after antigen challenge. However, a lymphocytic infiltrate and continued production of interferon-γ was observed in these animals. Thus, CD28 is not essential for the initial recruitment of lymphocytes into antigen-challenged airways but critically regulates the allergic T-helper 2 phenotype. We next determined by polymerase chain reaction and flow cytometry that CD80 and CD86 molecules are constitutively expressed in the naive murine lung and on eosinophils in the allergic lung, suggesting a potential important role for both ligands in the development of asthma. Combined anti-CD80/anti-CD86 treatment throughout the antigen challenge period fully blocked the development of allergic airways, whereas a partial reduction was observed in mice treated with either anti-CD80 or anti-CD86 antibody alone. However, only anti-CD86 blocked systemic IgE production. Therefore, signaling through either CD80 or CD86 is sufficient to generate a partial local allergic response, whereas CD86 costimulation is essential to induce systemic allergic (IgE) reactions. Finally, combined anti-B7 monoclonal antibody treatment after sensitization reduced airway eosinophilia and interleukin (IL)-4/IL-5 cytokine secretion consistent with an ongoing role for CD28/B7 interactions in the effector phase of the disease. These results emphasize the importance of differential B7 expression on different cells and in different organs on subsequent CD28/B7-mediated immune events, including the potential for CD28/B7 blockade in the treatment of atopic airway disease in people.
Details
- Title: Subtitle
- CD28 Interactions with Either CD80 or CD86 Are Sufficient to Induce Allergic Airway Inflammation in Mice
- Creators
- Mudit Mathur - May InstituteKarin HerrmannYimin QinFunda GulmenXiantang LiRebecca KriminsJoel WeinstockDavid ElliottJeffrey A. BluestonePhilip Padrid
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.21(4), pp.498-509
- DOI
- 10.1165/ajrcmb.21.4.3714
- PMID
- 10502560
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Language
- English
- Date published
- 10/01/1999
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984359926202771
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