Cyclosporin A attenuates genetic airway hyperresponsiveness in mice but not through inhibition of CD4+ or CD8+ T cells.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Cyclosporin A attenuates genetic airway hyperresponsiveness in mice but not through inhibition of CD4+ or CD8+ T cells.

Am J Respir Cell Mol Biol. 1996 Jun;14(6):627-34. Unique Identifier : AIDSLINE MED/96258776
Ewart SL; Gavett SH; Margolick J; Wills-Karp M; Department of Anesthesiology, Johns Hopkins Medical Institutions,; Baltimore, Maryland, USA.

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 micrograms, i.p.) or anti-CD8+ monoclonal antibody (J1.2, 500 micrograms; or YTS169.4, 150 micrograms, 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.

Keywords: Acetylcholine/PHARMACOLOGY Animal Antibodies, Monoclonal Biological Markers Bronchial Hyperreactivity/DRUG THERAPY/IMMUNOLOGY/ *PHYSIOPATHOLOGY Cyclosporine/*PHARMACOLOGY CD4-Positive T-Lymphocytes/*IMMUNOLOGY CD8-Positive T-Lymphocytes/*IMMUNOLOGY Disease Models, Animal Dose-Response Relationship, Drug Flow Cytometry Leukocyte Count Lung/CYTOLOGY/IMMUNOLOGY Lymphocyte Subsets/CYTOLOGY Male Mice Mice, Inbred A Mice, Inbred C3H Spleen/CYTOLOGY/DRUG EFFECTS Support, U.S. Gov't, P.H.S. Time Factors JOURNAL ARTICLE
961030
M96A1463

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