Am. J. Respir. Cell Mol. Biol., Vol 14, No. 6, Jun 1996, 627-634.
Cyclosporin A attenuates genetic airway hyperresponsiveness in mice but not through inhibition of CD4+ or CD8+ T cells
SL Ewart, SH Gavett, J Margolick and M Wills-Karp
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
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.
