Interferon‐γ‐dependent inhibition of late allergic airway responses and eosinophilia by CD8+γδ T cells

Abstract

We have previously shown that CD8⁺γδ T cells decrease late allergic airway responses, airway eosinophilia, T helper 2 cytokine expression and increase interferon-γ (IFN-γ) expression. We hypothesized that the effects of CD8⁺γδ T cells were IFN-γ mediated. Brown Norway rats were sensitized to ovalbumin on day 1. Cervical lymph node CD8⁺γδ T cells from sensitized animals were treated with antisense oligodeoxynucleotide (5 µmol/l) to inhibit IFN-γ synthesis or control oligodeoxynucleotide and 3·5 × 10⁴ CD8⁺γδ T cells were injected intraperitoneally into sensitized recipients on day 13. Rats were challenged with aerosolized ovalbumin on day 15 and lung resistance was monitored over an 8 hr period, after which bronchoalveolar lavage was performed. Control oligodeoxynucleotide treated γδ T cells decreased late airway responses and eosinophilia in bronchoalveolar lavage. There was a complete recovery of late airway responses and a partial recovery of airway eosinophilia in recipients of antisense oligodeoxynucleotide treated cells. Macrophage ingestion of eosinophils was frequent in rats administered γδT cells but reduced in recipients of antisense oligodeoxynucleotide treated cells. These results indicate that CD8⁺γδ T cells inhibit late airway responses and airway eosinophilia through the secretion of IFN-γ. Defective or altered γδ T-cell function may account for some forms of allergic asthma.