CD80 Costimulation Is Essential for the Induction of Airway Eosinophilia
نویسندگان
چکیده
CD80 and CD86 (B7-1 and B7-2) are the ligands on antigen-presenting cells (APCs) which bind CD28 and deliver the costimulatory signals necessary for T cell activation. The reasons for the existence of two CD28 binding molecules are not well understood. We created a mutant version of CTLA4-Ig that could selectively bind CD80 and block CD28-CD80 interaction but leave CD28-CD86 binding intact. CD80 blockade prevented antigen-induced accumulation of eosinophils and lymphocytes in the lung of immunized mice, but did not block antigen induced systemic blood eosinophilia or IgE antibody production. No preferential expression of CD80 could be demonstrated on a population of lung APC consisting mainly of macrophages. These results indicate that CD80 costimulation is not necessary for the induction of Th2 immune responses but rather for the maintenance or amplification of lung inflammatory responses.
منابع مشابه
CD80 costimulation is required for Th2 cell cytokine production but not for antigen-specific accumulation and migration into the lung.
The CD28 ligands CD80 and CD86 are expressed on APC, and both provide costimulatory function. However, the reason for the expression of two separate CD28 ligands remains unclear. We have previously shown that blockade of CD80 costimulation by Y100F-Ig, a CTL-associated Ag-4 (CTLA4)-Ig mutant that does not bind CD86, inhibits the development of lung inflammatory immune responses, but does not af...
متن کاملCD28 interactions with either CD80 or CD86 are sufficient to induce allergic airway inflammation in mice.
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. Un...
متن کاملCostimulation through CD86 is involved in airway antigen-presenting cell and T cell responses to allergen in atopic asthmatics.
Atopic allergic asthma is characterized by activation of Th2-type T cells in the bronchial mucosa. Previous reports have suggested an important role for costimulation through the CD28/CTLA4-CD80/CD86 pathway in allergen activation of T cells in animal models of inhaled allergen challenge. However, human allergen-specific lines and clones were reported to be costimulation independent. We therefo...
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Dendritic cells are believed to play an essential role in regulating the balance between immunogenic and tolerogenic responses to mucosal Ags by controlling T cell differentiation and activation via costimulatory and coinhibitory signals. The CD28/CTLA-4-CD80/CD86 signaling pathway appears to be one of the most important regulators of T cell responses but its exact role in responses to orally a...
متن کاملExpression of CD80 and CD86 on T lymphocytes and monocytes of asthmatic children
INTRODUCTION The concept of costimulation has changed the way of understanding how T cells recognise and respond to antigens . The current model of T cell activation requires two signals: Signal 1: It is only an initiation event. It requires T cell receptor recognition and binding to antigen presented by antigen presenting cells. However this signal alone is necessary but not sufficient to indu...
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ورودعنوان ژورنال:
- The Journal of Experimental Medicine
دوره 185 شماره
صفحات -
تاریخ انتشار 1997