IFN-γ secretion by CD8+T cells inhibits allergen-induced airway eosinophilia but not late airway responses

Abstract

Background: CD8+ T cells can suppress allergen-induced late airway responses (LARs) and airway inflammation. Objective: To test the hypothesis that the suppression of LARs and airway eosinophilia by CD8+ T cells is IFN-γ mediated, we tested the effects of adoptively transferred CD8+ T cells, in which IFN-γ synthesis was inhibited by an antisense (AS) oligodeoxynucleotide (ODN), on the airway responses of a rat model of allergic asthma. Methods: CD8+ T cells were harvested from the cervical lymph nodes of ovalbumin (OVA)-sensitized Brown Norway rats for administration to other actively sensitized syngeneic rats. CD8+ T cells (2 × 106) were incubated for 6 hours with 2 μmol/L AS ODN or sense ODN and were injected intraperitoneally into recipients; inhibition of IFN-γ expression in vitro by AS ODN was shown by means of flow cytometry. Two days later, rats were challenged with aerosolized OVA. Results: OVA-induced LAR and bronchoalveolar lavage (BAL) fluid eosinophilia were suppressed by sense ODN-treated CD8+ T cells. IFN-γ expression in BAL cells was elevated in these animals. IFN-γ expression in BAL cells was at control levels in recipients of AS ODN-treated CD8+ cells, confirming the success of the AS treatment in vivo. BAL eosinophilia was also largely restored in the AS ODN treatment group. In contrast, the CD8+ T cell-induced suppression of the LAR was not significantly affected by AS ODN pretreatment. Conclusions: These results indicate that CD8+ T cells inhibit airway eosinophilla through secretion of IFN-γ but may suppress the LAR by means of other mechanisms. © 2002 Elsevier Science Ltd. All rights reserved.