TY - JOUR
T1 - B7RP-1 is not required for the generation of Th2 responses in a model of allergic airway inflammation but is essential for the induction of inhalation tolerance
AU - Gajewska, Beata U.
AU - Tafuri, Anna
AU - Świrski, Filip K.
AU - Walker, Tina
AU - Johnson, Jill R.
AU - Shea, Theresa
AU - Shahinian, Arda
AU - Goncharova, Susanna
AU - Mak, Tak W.
AU - Stämpfli, Martin R.
AU - Jordana, Manel
PY - 2005/3/1
Y1 - 2005/3/1
N2 - The recently described ICOS-B7RP-1 costimulatory pathway has been implicated in the generation of effector Th2 responses and, hence, has become an attractive therapeutic target for allergic diseases. In the present study, we used B7KP-1-deficient mice to investigate the role of B7RP-1 in the generation and maintenance of Th2 responses in a model of mucosal allergic airway inflammation. We found that exposure of B7RP-1 knockout mice to aerosolized OVA in the context of GM-CSF leads to airway eosinophilic inflammation. This response was long lasting because rechalleage of mice with the same Ag recapitulated airway eosinophilia. Moreover, significant expression of T1/ST2 on T cells and production of Th2-affiliated cytokines (IL-5, IL-4, and IL-13) and Igs (IgE and IgG1) conclusively demonstrate the generation of a Th2 response in the absence of B7RP-1. In audition, expression of two major Th2-associated costimulatory molecules-CD28 and ICOS-indicates T cell activation in the absence of B7RP-1 signaling. Finally, B7RP-1 knockout mice are resistant to the induction of inhalation tolerance as indicated by the sustained eostaophilia in the lung and IL-5 production. In summary, our results demonstrate that in a model of mucosal allergic sensitization, the ICOS-B7RP-1 pathway is redundant for the generation of Th2 responses but essential for the induction of inhalation tolerance.
AB - The recently described ICOS-B7RP-1 costimulatory pathway has been implicated in the generation of effector Th2 responses and, hence, has become an attractive therapeutic target for allergic diseases. In the present study, we used B7KP-1-deficient mice to investigate the role of B7RP-1 in the generation and maintenance of Th2 responses in a model of mucosal allergic airway inflammation. We found that exposure of B7RP-1 knockout mice to aerosolized OVA in the context of GM-CSF leads to airway eosinophilic inflammation. This response was long lasting because rechalleage of mice with the same Ag recapitulated airway eosinophilia. Moreover, significant expression of T1/ST2 on T cells and production of Th2-affiliated cytokines (IL-5, IL-4, and IL-13) and Igs (IgE and IgG1) conclusively demonstrate the generation of a Th2 response in the absence of B7RP-1. In audition, expression of two major Th2-associated costimulatory molecules-CD28 and ICOS-indicates T cell activation in the absence of B7RP-1 signaling. Finally, B7RP-1 knockout mice are resistant to the induction of inhalation tolerance as indicated by the sustained eostaophilia in the lung and IL-5 production. In summary, our results demonstrate that in a model of mucosal allergic sensitization, the ICOS-B7RP-1 pathway is redundant for the generation of Th2 responses but essential for the induction of inhalation tolerance.
UR - http://www.scopus.com/inward/record.url?scp=20044387031&partnerID=8YFLogxK
UR - https://www.jimmunol.org/content/174/5/3000/tab-article-info
U2 - 10.4049/jimmunol.174.5.3000
DO - 10.4049/jimmunol.174.5.3000
M3 - Article
C2 - 15728513
AN - SCOPUS:20044387031
SN - 0022-1767
VL - 174
SP - 3000
EP - 3005
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -