CYCLOSPORINE-A ATTENUATES GENETIC AIRWAY HYPERRESPONSIVENESS IN MICE BUT NOT THROUGH INHIBITION OF CD4-CELLS( OR CD8+ T)

We examined the influence of T lymphocytes on genetically determined a irway 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 treat ment 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-stimulat ed airway responsiveness, assessed by the time-integrated peak inspira tory pressure (APTI) compared with C3H/HeJ control mice. ACh-induced A PTI 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 deple ted T-cell subsets with either rat anti-mouse CD4+ (L3T4) monoclonal a ntibody (GK1.5, 500 mu g, i.p.) or anti-CD8+ monoclonal antibody (J1.2 , 500 mu g; or YTS169.4, 150 mu g, ip) and assessed airway responsiven ess. No significant change in airway responsiveness was detected in ei ther strain after CD4+ or CD8+ T-cell depletion. Thus, although CsA ad ministration attenuated spleen cell activation and was associated with a marked attenuation of airway responsiveness in mice with geneticall y hyperresponsive airways, CD4+ and CD8+ T cells do not appear to medi ate this response. Ewart, S. L., S. H. Gavett, J. Margolick, and M. Wi lls-Karp. 1996, Cyclosporin A attenuates genetic airway hyperresponsiv eness in mice but not through inhibition of CD4+ or CD8+ T cells.