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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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Treatment with Y100F-Ig inhibits lung (A) but not blood  (B) eosinophilia in OVA-immunized, airway-challenged mice. C57BL/6  mice were primed twice i.p. with 2 μg OVA in alum adjuvant on day 0  and day 10 then given an intranasal challenge with 100 μg OVA in PBS 4  d after the last i.p. immunization. BAL fluid was collected 4 d after intranasal challenge. Differential cell counts were made on BAL cytospins and  blood smears stained with Diff-Quik. Mice were treated i.p. with 400 μg  of either CTLA4-Ig, Y100F-Ig or L6-Ig every 48 h. Values represent the  mean ± SE for groups of 5–7 mice. Results shown are representative of  four (A) and two (B) experiments.
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Figure 2: Treatment with Y100F-Ig inhibits lung (A) but not blood (B) eosinophilia in OVA-immunized, airway-challenged mice. C57BL/6 mice were primed twice i.p. with 2 μg OVA in alum adjuvant on day 0 and day 10 then given an intranasal challenge with 100 μg OVA in PBS 4 d after the last i.p. immunization. BAL fluid was collected 4 d after intranasal challenge. Differential cell counts were made on BAL cytospins and blood smears stained with Diff-Quik. Mice were treated i.p. with 400 μg of either CTLA4-Ig, Y100F-Ig or L6-Ig every 48 h. Values represent the mean ± SE for groups of 5–7 mice. Results shown are representative of four (A) and two (B) experiments.

Mentions: Eosinophil infiltration into the airways of OVA-immunized, airway challenged mice was blocked by treatment with either CTLA4-Ig or Y100F-Ig (Fig. 2 A). The numbers of lymphocytes in the BAL were also strongly diminished in these two groups compared to L6-Ig. Because in vivo injection of anti-CD4 or anti-IL-5 Ab before the intranasal challenge completely abrogates the appearance of eosinophils in the BAL (18), we interpreted the result in Fig. 2 A as suggesting that both CTLA-4 Ig and Y100F-Ig interfere with the generation of IL-5-producing Th2 cells. Indeed, CTLA4-Ig also inhibited the OVA-induced appearance of eosinophils in the blood (Fig. 2 B). This response precedes accumulation of eosinophils in the lung, and is also dependent on IL-5 production (19). Surprisingly, however, Y100F-Ig failed to inhibit blood eosinophilia, with levels being comparable in Y100F-Ig– and L6Ig–treated mice (Fig. 2 B). Thus, CTLA4-Ig and Y100F-Ig have different effects on systemic eosinophilia. CTLA4-Ig most likely acts on IL-5 secretion by T cells, and therefore blocks all eosinophil responses. The effects of Y100F-Ig are more selective in that it prevents the accumulation of eosinophils in the lung without blocking systemic IL-5 secretion.


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 Y100F-Ig inhibits lung (A) but not blood  (B) eosinophilia in OVA-immunized, airway-challenged mice. C57BL/6  mice were primed twice i.p. with 2 μg OVA in alum adjuvant on day 0  and day 10 then given an intranasal challenge with 100 μg OVA in PBS 4  d after the last i.p. immunization. BAL fluid was collected 4 d after intranasal challenge. Differential cell counts were made on BAL cytospins and  blood smears stained with Diff-Quik. Mice were treated i.p. with 400 μg  of either CTLA4-Ig, Y100F-Ig or L6-Ig every 48 h. Values represent the  mean ± SE for groups of 5–7 mice. Results shown are representative of  four (A) and two (B) experiments.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196101&req=5

Figure 2: Treatment with Y100F-Ig inhibits lung (A) but not blood (B) eosinophilia in OVA-immunized, airway-challenged mice. C57BL/6 mice were primed twice i.p. with 2 μg OVA in alum adjuvant on day 0 and day 10 then given an intranasal challenge with 100 μg OVA in PBS 4 d after the last i.p. immunization. BAL fluid was collected 4 d after intranasal challenge. Differential cell counts were made on BAL cytospins and blood smears stained with Diff-Quik. Mice were treated i.p. with 400 μg of either CTLA4-Ig, Y100F-Ig or L6-Ig every 48 h. Values represent the mean ± SE for groups of 5–7 mice. Results shown are representative of four (A) and two (B) experiments.
Mentions: Eosinophil infiltration into the airways of OVA-immunized, airway challenged mice was blocked by treatment with either CTLA4-Ig or Y100F-Ig (Fig. 2 A). The numbers of lymphocytes in the BAL were also strongly diminished in these two groups compared to L6-Ig. Because in vivo injection of anti-CD4 or anti-IL-5 Ab before the intranasal challenge completely abrogates the appearance of eosinophils in the BAL (18), we interpreted the result in Fig. 2 A as suggesting that both CTLA-4 Ig and Y100F-Ig interfere with the generation of IL-5-producing Th2 cells. Indeed, CTLA4-Ig also inhibited the OVA-induced appearance of eosinophils in the blood (Fig. 2 B). This response precedes accumulation of eosinophils in the lung, and is also dependent on IL-5 production (19). Surprisingly, however, Y100F-Ig failed to inhibit blood eosinophilia, with levels being comparable in Y100F-Ig– and L6Ig–treated mice (Fig. 2 B). Thus, CTLA4-Ig and Y100F-Ig have different effects on systemic eosinophilia. CTLA4-Ig most likely acts on IL-5 secretion by T cells, and therefore blocks all eosinophil responses. The effects of Y100F-Ig are more selective in that it prevents the accumulation of eosinophils in the lung without blocking systemic IL-5 secretion.

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