CD8+ T cells are not sufficient for induction of tolerance in a murine model of ovalbumin-induced allergic airway diease (P3209)

Abstract

Abstract In our biphasic ovalbumin (OVA)-induced murine model of allergic airway disease (AAD), short-term daily OVA aerosol exposure for 7 to 14 days results in AAD whereas continued exposure for 42 days leads to resolution of disease and local inhalational tolerance (LIT). We have previously demonstrated that OVA-specific CD8+ T cells exhibit plasticity from a pro-inflammatory phenotype at AAD (increased granzyme B and IFN γ) to a suppressive phenotype (NKG2A+, decreased granzyme B and IFN γ) at LIT. Since the role of CD8+ T cells in asthma remains unclear we used our biphasic model to determine whether CD8+ T cells can induce suppression of AAD. We isolated CD8+ T cells from HLN of LIT mice and adoptively transferred them into sensitized mice and challenged with OVA aerosols to induce AAD. We observed no differences in lung histology and total eosinophils in bronchoalveolar lavage of mice that were transferred with CD8+ T cells as compared to mice transferred with naïve T cells (n=5, p > 0.05). We further investigated localization of OVA-specific CD8+ T cells in HLN (confocal microscopy) and showed that these cells do not localize in follicular regions of HLN at LIT unlike what we have previously described with the co-localization of Foxp3+ Tregs and Bregs. Thus, we have demonstrated that CD8+ T cells are not sufficient for suppression of AAD and do not preferentially localize in follicles of HLN at LIT.