Cyclosporin A Attenuates Genetic Airway Hyperresponsiveness in Mice but Not through Inhibition of CD4+ or CD8+ T Cells

Susan L. Ewart, Stephen H. Gavett, Joseph Margolick, Marsha Wills-Karp

Research output: Contribution to journalArticlepeer-review

Abstract

We examined the influence of T lymphocytes on genetically determined airway hyperresponsiveness to acetylcholine (ACh) in mice. A/J and C3H/HeJ mice were treated with the T-cell suppressant cyclosporin A [(CsA) 25 to 100 mg/kg, intraperitoneally (i.p.), for 5 to 10 days], whereas control animals received the vehicle or remained untreated. CsA treatment induced a dose-dependent suppression of mitogen-stimulated spleen cell proliferation which was equivalent between the two strains. A/J control animals demonstrated approximately 8-fold greater ACh-stimulated airway responsiveness, assessed by the time-integrated peak inspiratory pressure (APTI) compared with C3H/HeJ control mice. ACh-induced APTI was attenuated by CsA in a dose- and time-dependent manner in the A/J strain; no significant changes occurred in the C3H/HeJ strain. To determine whether lymphocyte subtypes mediated this response, we depleted T-cell subsets with either rat anti-mouse CD4+ (L3T4) monoclonal antibody (GK1.5, 500 μg, i.p.) or anti-CD8+ monoclonal antibody (J1.2, 500 μg; or YTS169.4, 150 μg, i.p.) and assessed airway responsiveness. No significant change in airway responsiveness was detected in either strain after CD4+ or CD8+ T-cell depletion. Thus, although CsA administration attenuated spleen cell activation and was associated with a marked attenuation of airway responsiveness in mice with genetically hyperresponsive airways, CD4+ and CD8+ T cells do not appear to mediate this response.

Original languageEnglish (US)
Pages (from-to)627-634
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume14
Issue number6
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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