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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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Related in: MedlinePlus

Treatment with  CTLA4-Ig, but not Y100F-Ig,  inhibits the production of OVAspecific IgG1, IgG2a and IgE.  Mice were treated with CTLA4Ig, Y100F-Ig or L6-Ig and  subjected to a protocol of OVA  immunization and airway challenge as detailed in Fig. 2. Serum  was collected at the time of death  and OVA-specific antibody levels determined by ELISA. Values  represent serum antibody titers  for individual mice. Shown are  the results of two pooled experiments.
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Figure 3: Treatment with CTLA4-Ig, but not Y100F-Ig, inhibits the production of OVAspecific IgG1, IgG2a and IgE. Mice were treated with CTLA4Ig, Y100F-Ig or L6-Ig and subjected to a protocol of OVA immunization and airway challenge as detailed in Fig. 2. Serum was collected at the time of death and OVA-specific antibody levels determined by ELISA. Values represent serum antibody titers for individual mice. Shown are the results of two pooled experiments.

Mentions: To determine the effect of CD80 costimulation on Ab production OVA-specific IgG and IgE titers were measured in CTLA4-Ig–, Y100F-Ig–, and L6-Ig–treated mice. As expected all Ab isotypes were lowered by CTLA4-Ig treatment (Fig. 3). Levels of IgG1, IgG2a and IgE were similar in Y100F-Ig– and L6-Ig–treated mice (Fig. 3). This result indicates that OVA-specific T cells that can deliver help to B cells have been generated in Y100F-Ig–treated mice. These T cells must be capable of IL-4 secretion in vivo since the development of an Ag-specific IgE response has been shown to be entirely dependent upon production of IL-4 (20, 21). The high levels of IgG1 and IgE, and low levels of IgG2a in Y100F-Ig– and L6-Ig–treated mice (Fig. 3) indicated that both groups generated a good Th2 response but little or no Th1 response.


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)

Treatment with  CTLA4-Ig, but not Y100F-Ig,  inhibits the production of OVAspecific IgG1, IgG2a and IgE.  Mice were treated with CTLA4Ig, Y100F-Ig or L6-Ig and  subjected to a protocol of OVA  immunization and airway challenge as detailed in Fig. 2. Serum  was collected at the time of death  and OVA-specific antibody levels determined by ELISA. Values  represent serum antibody titers  for individual mice. Shown are  the results of two pooled experiments.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Treatment with CTLA4-Ig, but not Y100F-Ig, inhibits the production of OVAspecific IgG1, IgG2a and IgE. Mice were treated with CTLA4Ig, Y100F-Ig or L6-Ig and subjected to a protocol of OVA immunization and airway challenge as detailed in Fig. 2. Serum was collected at the time of death and OVA-specific antibody levels determined by ELISA. Values represent serum antibody titers for individual mice. Shown are the results of two pooled experiments.
Mentions: To determine the effect of CD80 costimulation on Ab production OVA-specific IgG and IgE titers were measured in CTLA4-Ig–, Y100F-Ig–, and L6-Ig–treated mice. As expected all Ab isotypes were lowered by CTLA4-Ig treatment (Fig. 3). Levels of IgG1, IgG2a and IgE were similar in Y100F-Ig– and L6-Ig–treated mice (Fig. 3). This result indicates that OVA-specific T cells that can deliver help to B cells have been generated in Y100F-Ig–treated mice. These T cells must be capable of IL-4 secretion in vivo since the development of an Ag-specific IgE response has been shown to be entirely dependent upon production of IL-4 (20, 21). The high levels of IgG1 and IgE, and low levels of IgG2a in Y100F-Ig– and L6-Ig–treated mice (Fig. 3) indicated that both groups generated a good Th2 response but little or no Th1 response.

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