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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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Y100F-Ig binds to murine CD80 but not CD86. Y100F-Ig  (circles) and wild-type CTLA4-Ig (squares) were incubated with Chinese  Hamster Ovary (CHO) cells stably transfected with murine CD80 or  CD86 and binding determined by FACS® analysis.
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Figure 1: Y100F-Ig binds to murine CD80 but not CD86. Y100F-Ig (circles) and wild-type CTLA4-Ig (squares) were incubated with Chinese Hamster Ovary (CHO) cells stably transfected with murine CD80 or CD86 and binding determined by FACS® analysis.

Mentions: We have previously shown that amino acid residues in the conserved MYPPPY motif of CTLA4-Ig are critical for the binding of CTLA4-Ig to CD80 (17). Mutation of the first tyrosine in this motif (Tyr 100) to alanine resulted in reduced binding to CD80 but abolished binding to CD86 (5). However, mutation of Tyr 100 to phenylalanine resulted in a molecule (Y100F-Ig), which retained wild-type binding to CD80, but with no apparent binding to CD86. As shown in Fig. 1, FACS® analysis demonstrated that Y100F-Ig and CTLA4-Ig bind equally well to CHO cells expressing murine CD80. In contrast, binding of Y100F-Ig to CHO cells expressing murine CD86 was undetectable even at concentrations as high as 100 μg/ml. These data confirm that Y100F-Ig can be used to selectively block CD80-mediated costimulation to T cells.


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)

Y100F-Ig binds to murine CD80 but not CD86. Y100F-Ig  (circles) and wild-type CTLA4-Ig (squares) were incubated with Chinese  Hamster Ovary (CHO) cells stably transfected with murine CD80 or  CD86 and binding determined by FACS® analysis.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Y100F-Ig binds to murine CD80 but not CD86. Y100F-Ig (circles) and wild-type CTLA4-Ig (squares) were incubated with Chinese Hamster Ovary (CHO) cells stably transfected with murine CD80 or CD86 and binding determined by FACS® analysis.
Mentions: We have previously shown that amino acid residues in the conserved MYPPPY motif of CTLA4-Ig are critical for the binding of CTLA4-Ig to CD80 (17). Mutation of the first tyrosine in this motif (Tyr 100) to alanine resulted in reduced binding to CD80 but abolished binding to CD86 (5). However, mutation of Tyr 100 to phenylalanine resulted in a molecule (Y100F-Ig), which retained wild-type binding to CD80, but with no apparent binding to CD86. As shown in Fig. 1, FACS® analysis demonstrated that Y100F-Ig and CTLA4-Ig bind equally well to CHO cells expressing murine CD80. In contrast, binding of Y100F-Ig to CHO cells expressing murine CD86 was undetectable even at concentrations as high as 100 μg/ml. These data confirm that Y100F-Ig can be used to selectively block CD80-mediated costimulation to T cells.

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