B7-CD28/CTLA-4 Costimulatory Pathways Are Required for the Development of T Helper Cell 2-Mediated Allergic Airway Responses to Inhaled Antigens

Andrea Keane-Myers, William C. Gause, Peter S. Linsley, Shen Jue Chen, Marsha Wills-Karp

Research output: Contribution to journalArticle

Abstract

We have previously demonstrated that the development of allergen-induced airway hyperresponsiveness in a murine model is CD4+ T cell dependent. In the present study, we examined the role of the B7/CD28-CTLA4 costimulatory T cell activation pathway in the pathogenesis of allergen-induced airway hyperresponsiveness in this murine model. Sensitized A/J mice develop significant increases in airway responsiveness, bronchoalveolar lavage eosinophils, serum IgE levels, and Th2-associated cytokine production following aspiration challenge with OVA. Administration of CTLA4-Ig either before Ag sensitization or before pulmonary Ag challenge abolished Ag-induced airway hyperresponsiveness and pulmonary eosinophilia. Examination of cytokine protein levels in the bronchoalveolar lavage showed a significant decrease in the level of the Th2 cytokine, IL-4, after CTLA4-Ig treatment either before sensitization or before challenge, with no significant change in the concentration of the Th1 cytokine, IFN-γ. Further, the Ag-specific Ab isotypes IgG1 and IgE were significantly decreased in animals treated with CTLA4-Ig before challenge, while there was no significant change in the IgG2a Ab isotype. These data demonstrate that administration of CTLA4-Ig is effective in ablating allergen-induced airway dysfunction concomitant with a significant reduction in the Th2 response. We conclude that B7/CD28-CTLA-4 costimulation is required for the development of many of the immunologic and physiologic features of asthma, possibly by promoting a pathologic type 2-associated response.

Original languageEnglish (US)
Pages (from-to)2042-2049
Number of pages8
JournalJournal of Immunology
Volume158
Issue number5
StatePublished - Mar 1 1997

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Th2 Cells
Allergens
Cytokines
Antigens
Bronchoalveolar Lavage
Immunoglobulin E
Pulmonary Eosinophilia
T-Lymphocytes
Eosinophils
Interleukin-4
Asthma
Immunoglobulin G
Lung
Abatacept
Serum
Proteins
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

B7-CD28/CTLA-4 Costimulatory Pathways Are Required for the Development of T Helper Cell 2-Mediated Allergic Airway Responses to Inhaled Antigens. / Keane-Myers, Andrea; Gause, William C.; Linsley, Peter S.; Chen, Shen Jue; Wills-Karp, Marsha.

In: Journal of Immunology, Vol. 158, No. 5, 01.03.1997, p. 2042-2049.

Research output: Contribution to journalArticle

Keane-Myers, Andrea ; Gause, William C. ; Linsley, Peter S. ; Chen, Shen Jue ; Wills-Karp, Marsha. / B7-CD28/CTLA-4 Costimulatory Pathways Are Required for the Development of T Helper Cell 2-Mediated Allergic Airway Responses to Inhaled Antigens. In: Journal of Immunology. 1997 ; Vol. 158, No. 5. pp. 2042-2049.
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