Anti-CD86 (B7.2) Treatment abolishes allergic airway hyperresponsiveness in mice

Angela Franciska Haczku, Katsuyuki Takeda, Imre Redai, Eckard Hamelmann, Gregory Cieslewicz, Anthony Joetham, Joan Loader, James J. Lee, Charles Irvin, Erwin W. Gelfand

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Allergic sensitization in asthma develops as a consequence of complex interactions between T cells and antigen-presenting cells. We have developed several in vivo models to study allergen-specific T cell and B cell function and their relevance to allergic airway hyperresponsiveness (AHR), focusing on the role of the costimulatory molecules CD80 and CD86. Treatment of mice with anti-CD86, but not anti-CD80, significantly inhibited increased serum levels of ovalbumin (OA)-specific IgE and IgG1, airway eosinophilia, and AHR both after 10 d of OA aerosol exposure (in the absence of adjuvant) and after intraperitoneal sensitization followed by repeated airway challenges. Inhibition of AHR was associated with decreased IL-4 and IL-5 levels in the BAL fluid of sensitized mice, suggesting impaired Th2 function in anti-CD86- treated animals. This effect was not seen when mice received treatment only before allergen challenge, indicating that anti-CD86 acts through inhibition of allergic sensitization and not simply by inhibiting the influx of inflammatory cells. These data suggest that the CD86 costimulatory ligand plays a major role in the development of allergic inflammation and AHR in allergen-challenged mice. Further, this study demonstrates that T-B cell interactions during allergic sensitization are amenable to therapeutic manipulation and that selective blockade of accessory signals can be an effective means for modulating distinct T cell functions.

Original languageEnglish (US)
Pages (from-to)1638-1643
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume159
Issue number5 I
StatePublished - 1999
Externally publishedYes

Fingerprint

Allergens
Ovalbumin
T-Lymphocytes
B-Lymphocytes
Dimercaprol
Viral Tumor Antigens
Interleukin-5
Eosinophilia
Antigen-Presenting Cells
Aerosols
Cell Communication
Interleukin-4
Immunoglobulin E
Asthma
Immunoglobulin G
Ligands
Inflammation
Serum
Therapeutics

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Haczku, A. F., Takeda, K., Redai, I., Hamelmann, E., Cieslewicz, G., Joetham, A., ... Gelfand, E. W. (1999). Anti-CD86 (B7.2) Treatment abolishes allergic airway hyperresponsiveness in mice. American Journal of Respiratory and Critical Care Medicine, 159(5 I), 1638-1643.

Anti-CD86 (B7.2) Treatment abolishes allergic airway hyperresponsiveness in mice. / Haczku, Angela Franciska; Takeda, Katsuyuki; Redai, Imre; Hamelmann, Eckard; Cieslewicz, Gregory; Joetham, Anthony; Loader, Joan; Lee, James J.; Irvin, Charles; Gelfand, Erwin W.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 159, No. 5 I, 1999, p. 1638-1643.

Research output: Contribution to journalArticle

Haczku, AF, Takeda, K, Redai, I, Hamelmann, E, Cieslewicz, G, Joetham, A, Loader, J, Lee, JJ, Irvin, C & Gelfand, EW 1999, 'Anti-CD86 (B7.2) Treatment abolishes allergic airway hyperresponsiveness in mice', American Journal of Respiratory and Critical Care Medicine, vol. 159, no. 5 I, pp. 1638-1643.
Haczku, Angela Franciska ; Takeda, Katsuyuki ; Redai, Imre ; Hamelmann, Eckard ; Cieslewicz, Gregory ; Joetham, Anthony ; Loader, Joan ; Lee, James J. ; Irvin, Charles ; Gelfand, Erwin W. / Anti-CD86 (B7.2) Treatment abolishes allergic airway hyperresponsiveness in mice. In: American Journal of Respiratory and Critical Care Medicine. 1999 ; Vol. 159, No. 5 I. pp. 1638-1643.
@article{73ef0f2d383a4f5e87b14bb523c868a1,
title = "Anti-CD86 (B7.2) Treatment abolishes allergic airway hyperresponsiveness in mice",
abstract = "Allergic sensitization in asthma develops as a consequence of complex interactions between T cells and antigen-presenting cells. We have developed several in vivo models to study allergen-specific T cell and B cell function and their relevance to allergic airway hyperresponsiveness (AHR), focusing on the role of the costimulatory molecules CD80 and CD86. Treatment of mice with anti-CD86, but not anti-CD80, significantly inhibited increased serum levels of ovalbumin (OA)-specific IgE and IgG1, airway eosinophilia, and AHR both after 10 d of OA aerosol exposure (in the absence of adjuvant) and after intraperitoneal sensitization followed by repeated airway challenges. Inhibition of AHR was associated with decreased IL-4 and IL-5 levels in the BAL fluid of sensitized mice, suggesting impaired Th2 function in anti-CD86- treated animals. This effect was not seen when mice received treatment only before allergen challenge, indicating that anti-CD86 acts through inhibition of allergic sensitization and not simply by inhibiting the influx of inflammatory cells. These data suggest that the CD86 costimulatory ligand plays a major role in the development of allergic inflammation and AHR in allergen-challenged mice. Further, this study demonstrates that T-B cell interactions during allergic sensitization are amenable to therapeutic manipulation and that selective blockade of accessory signals can be an effective means for modulating distinct T cell functions.",
author = "Haczku, {Angela Franciska} and Katsuyuki Takeda and Imre Redai and Eckard Hamelmann and Gregory Cieslewicz and Anthony Joetham and Joan Loader and Lee, {James J.} and Charles Irvin and Gelfand, {Erwin W.}",
year = "1999",
language = "English (US)",
volume = "159",
pages = "1638--1643",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "5 I",

}

TY - JOUR

T1 - Anti-CD86 (B7.2) Treatment abolishes allergic airway hyperresponsiveness in mice

AU - Haczku, Angela Franciska

AU - Takeda, Katsuyuki

AU - Redai, Imre

AU - Hamelmann, Eckard

AU - Cieslewicz, Gregory

AU - Joetham, Anthony

AU - Loader, Joan

AU - Lee, James J.

AU - Irvin, Charles

AU - Gelfand, Erwin W.

PY - 1999

Y1 - 1999

N2 - Allergic sensitization in asthma develops as a consequence of complex interactions between T cells and antigen-presenting cells. We have developed several in vivo models to study allergen-specific T cell and B cell function and their relevance to allergic airway hyperresponsiveness (AHR), focusing on the role of the costimulatory molecules CD80 and CD86. Treatment of mice with anti-CD86, but not anti-CD80, significantly inhibited increased serum levels of ovalbumin (OA)-specific IgE and IgG1, airway eosinophilia, and AHR both after 10 d of OA aerosol exposure (in the absence of adjuvant) and after intraperitoneal sensitization followed by repeated airway challenges. Inhibition of AHR was associated with decreased IL-4 and IL-5 levels in the BAL fluid of sensitized mice, suggesting impaired Th2 function in anti-CD86- treated animals. This effect was not seen when mice received treatment only before allergen challenge, indicating that anti-CD86 acts through inhibition of allergic sensitization and not simply by inhibiting the influx of inflammatory cells. These data suggest that the CD86 costimulatory ligand plays a major role in the development of allergic inflammation and AHR in allergen-challenged mice. Further, this study demonstrates that T-B cell interactions during allergic sensitization are amenable to therapeutic manipulation and that selective blockade of accessory signals can be an effective means for modulating distinct T cell functions.

AB - Allergic sensitization in asthma develops as a consequence of complex interactions between T cells and antigen-presenting cells. We have developed several in vivo models to study allergen-specific T cell and B cell function and their relevance to allergic airway hyperresponsiveness (AHR), focusing on the role of the costimulatory molecules CD80 and CD86. Treatment of mice with anti-CD86, but not anti-CD80, significantly inhibited increased serum levels of ovalbumin (OA)-specific IgE and IgG1, airway eosinophilia, and AHR both after 10 d of OA aerosol exposure (in the absence of adjuvant) and after intraperitoneal sensitization followed by repeated airway challenges. Inhibition of AHR was associated with decreased IL-4 and IL-5 levels in the BAL fluid of sensitized mice, suggesting impaired Th2 function in anti-CD86- treated animals. This effect was not seen when mice received treatment only before allergen challenge, indicating that anti-CD86 acts through inhibition of allergic sensitization and not simply by inhibiting the influx of inflammatory cells. These data suggest that the CD86 costimulatory ligand plays a major role in the development of allergic inflammation and AHR in allergen-challenged mice. Further, this study demonstrates that T-B cell interactions during allergic sensitization are amenable to therapeutic manipulation and that selective blockade of accessory signals can be an effective means for modulating distinct T cell functions.

UR - http://www.scopus.com/inward/record.url?scp=0032914146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032914146&partnerID=8YFLogxK

M3 - Article

C2 - 10228138

AN - SCOPUS:0032914146

VL - 159

SP - 1638

EP - 1643

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 5 I

ER -