CD8⁺ T cell-mediated airway hyperresponsiveness and inflammation is dependent on CD4⁺IL-4⁺ T cells

CD4⁺ T cells, particularly Th2 cells, play a pivotal role in allergic airway inflammation. However, the requirements for interactions between CD4⁺ and CD8⁺ T cells in airway allergic inflammation have not been delineated. Sensitized and challenged OT-1 mice in which CD8 ⁺ T cells expressing the transgene for the OVA_257-264 peptide (SIINFEKL) failed to develop airway hyperresponsiveness (AHR), airway eosinophilia, Th2 cytokine elevation, or goblet cell metaplasia. OT-1 mice that received naive CD4⁺IL-4⁺ T cells but not CD4 ⁺IL-4^- T cells before sensitization developed all of these responses to the same degree as wild-type mice. Moreover, recipients of CD4⁺IL-4⁺ T cells developed significant increases in the number of CD8⁺IL-13⁺ T cells in the lung, whereas sensitized OT-1 mice that received primed CD4⁺ T cells just before challenge failed to develop these responses. Sensitized CD8-deficient mice that received CD8⁺ T cells from OT-1 mice that received naive CD4 ⁺ T cells before sensitization increased AHR and eosinophil numbers in bronchoalveolar lavage fluid when challenged with allergen. In contrast, sensitized CD8-deficient mice receiving CD8⁺ T cells from OT-1 mice without CD4⁺ T cells developed reduced AHR and eosinophil numbers in bronchoalveolar lavage fluid when challenged. These data suggest that interactions between CD4⁺ and CD8⁺ T cells, in part through IL-4 during the sensitization phase, are essential to the development of CD8⁺IL-13⁺ T cell-dependent AHR and airway allergic inflammation.