The role of CD8(+) T cells in the development of allergic airway disease is controversial. On the one hand, CD8(+) T cells are known to inhibit the development of airway hyperreactivity (AHR) in murine models of asthma. In humans, IL-10-producing CD8(+) T cells were shown to act as regulatory cells, inhibiting both proliferation and cytokine secretion of T cells. On the other hand, CD8(+) T cells can promote IL-5-mediated eosinophilic airway inflammation and the development of AHR in animal models. To examine this, we investigated the role of CD8(+) T cells during the induction of allergen-induced AHR and demonstrated a protective effect of CD8(+) T cells. Depletion of CD8(+) T cells prior to the immunization led to increased Th2 responses and increased allergic airway disease. However, after development of AHR, CD8(+) T cells that infiltrated the lungs secreted high levels of IL-4, IL-5 and IL-10, but little IFN-gamma, whereas CD8(+) T cells in the peribronchial lymph nodes or spleen produced high levels of IFN-gamma, but little or no Th2 cytokines. These data demonstrate protective effects of CD8(+)T cells against the induction of immune responses and show a functional diversity of CD8(+) T cells in different compartments of sensitized mice.