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

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-gamma mediated, we tested the effects of adoptively transferred CD8(+) T cells, in which IFN-gamma 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 x 10(6)) were incubated for 6 hours with 2 mumol/L AS ODN or sense ODN and were injected intraperitoneally into recipients; inhibition of IFN-gamma 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-gamma expression in BAL cells was elevated in these animals. IFNgamma 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 eosinophilia through secretion of IFN-gamma but may suppress the LAR by means of other mechanisms.