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CD80 costimulation is essential for the induction of airway eosinophilia.

Harris N, Peach R, Naemura J, Linsley PS, Le Gros G, Ronchese F - J. Exp. Med. (1997)

Bottom Line: We created a mutant version of CTLA4-Ig that could selectively bind CD80 and block CD28-CD80 interaction but leave CD28-CD86 binding intact.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.

View Article: PubMed Central - PubMed

Affiliation: Malaghan Institute of Medical Research, Wellington School of Medicine, New Zealand.

ABSTRACT
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.

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CD86 is expressed on lung macrophages from OVA-immunized and airway-challenged mice. BAL cells were collected from mice  subjected to a protocol of OVA immunization and airway challenge as  detailed in Fig. 2 and CD80/CD86 expression determined by FACS®  analysis. Filled histogram, non-stained samples; empty histogram, samples  stained as indicated.
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Figure 4: CD86 is expressed on lung macrophages from OVA-immunized and airway-challenged mice. BAL cells were collected from mice subjected to a protocol of OVA immunization and airway challenge as detailed in Fig. 2 and CD80/CD86 expression determined by FACS® analysis. Filled histogram, non-stained samples; empty histogram, samples stained as indicated.

Mentions: It was possible that T cells capable of secreting both IL-4 and IL-5 could accumulate in the lung of Y100F-Ig–treated mice, but that once in the lung their further activation was blocked because of the preferential expression of CD80 ligands by local APC. This could lead to termination of the response in the lung due to lack of production of T cell– derived cytokines and chemotactic factors necessary for the amplification of the response. To address this we stained lung macrophages, isolated from OVA-immunized and airway challenged mice, with Abs to CD80 and CD86. Although CD80 was not detectable by FACS analysis, staining for CD86 was observed (Fig. 4). Other lung resident APC, such as dendritic cells, are also reported to express both CD80 and CD86 (22). Together, these results rule out the possibility that Y100F-Ig treatment can selectively block the activation of    T cell responses because of selective expression of CD80 ligands on local APC. This system differs from another disease model in which CD80 was the predominant costimulatory molecule expressed at the site of inflammation and in which CD80 blockade was effective (10).


CD80 costimulation is essential for the induction of airway eosinophilia.

Harris N, Peach R, Naemura J, Linsley PS, Le Gros G, Ronchese F - J. Exp. Med. (1997)

CD86 is expressed on lung macrophages from OVA-immunized and airway-challenged mice. BAL cells were collected from mice  subjected to a protocol of OVA immunization and airway challenge as  detailed in Fig. 2 and CD80/CD86 expression determined by FACS®  analysis. Filled histogram, non-stained samples; empty histogram, samples  stained as indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196101&req=5

Figure 4: CD86 is expressed on lung macrophages from OVA-immunized and airway-challenged mice. BAL cells were collected from mice subjected to a protocol of OVA immunization and airway challenge as detailed in Fig. 2 and CD80/CD86 expression determined by FACS® analysis. Filled histogram, non-stained samples; empty histogram, samples stained as indicated.
Mentions: It was possible that T cells capable of secreting both IL-4 and IL-5 could accumulate in the lung of Y100F-Ig–treated mice, but that once in the lung their further activation was blocked because of the preferential expression of CD80 ligands by local APC. This could lead to termination of the response in the lung due to lack of production of T cell– derived cytokines and chemotactic factors necessary for the amplification of the response. To address this we stained lung macrophages, isolated from OVA-immunized and airway challenged mice, with Abs to CD80 and CD86. Although CD80 was not detectable by FACS analysis, staining for CD86 was observed (Fig. 4). Other lung resident APC, such as dendritic cells, are also reported to express both CD80 and CD86 (22). Together, these results rule out the possibility that Y100F-Ig treatment can selectively block the activation of    T cell responses because of selective expression of CD80 ligands on local APC. This system differs from another disease model in which CD80 was the predominant costimulatory molecule expressed at the site of inflammation and in which CD80 blockade was effective (10).

Bottom Line: We created a mutant version of CTLA4-Ig that could selectively bind CD80 and block CD28-CD80 interaction but leave CD28-CD86 binding intact.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.

View Article: PubMed Central - PubMed

Affiliation: Malaghan Institute of Medical Research, Wellington School of Medicine, New Zealand.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus