当前位置： SCI文献检索 > AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY期刊下所有文献 > CD28 interactions with either CD80 or CD86 are sufficient to induce allergic airway inflammation in mice.

CD28 interactions with either CD80 or CD86 are sufficient to induce allergic airway inflammation in mice.

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-gamma 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.

journal_name

Am J Respir Cell Mol Biol

journal_title

American journal of respiratory cell and molecular biology

authors

Mathur M,Herrmann K,Qin Y,Gulmen F,Li X,Krimins R,Weinstock J,Elliott D,Bluestone JA,Padrid P

doi

10.1165/ajrcmb.21.4.3714

keywords:

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

498-509

issue

eissn

1044-1549

issn

1535-4989

journal_volume

pub_type

杂志文章

在线工具

CD28 interactions with either CD80 or CD86 are sufficient to induce allergic airway inflammation in mice.