Attenuation of allergen-induced responses in CCR6-/- mice is dependent upon altered pulmonary T lymphocyte activation

We have established a defect in CCR6(-/-) mice in response to a cockroach allergen airway challenge characterized by decreased IL-5 production, reduced CD4(+) T and B cells as well as decreased eosinophil accumulation. To determine the nature of the defect in CCR6(-/-) mice T lymphocyte populations from allergen-sensitized wild-type mice were transferred into sensitized CCR6(-/-) mice. The reconstituted response was characterized by an increase in IL-5 levels, eosinophil accumulation, and serum IgE levels in recipient CCR6(-/-) mice. Analysis of lymphocytes from draining lymph nodes of CCR6(+/+) and CCR6(-/-) sensitized or challenged mice demonstrated a significant decrease in IL-5 and IL-13 production in CCR6(-/-) mice. In contrast, the systemic response in allergen-rechallenged spleen cells demonstrated no significant alteration in allergen-induced cytokine production. Transfer of isolated splenic T lymphocytes from sensitized CCR6(+/+) mice induced airway hyperresponsiveness in wild-type but not CCR6(-/-) naive mice, suggesting that T cells alone were not sufficient to induce airway hyperresponsiveness in CCR6(-/-) mice. Additional analysis demonstrated decreased CD11c(+), CD11b(+) and CD11c, and B220 subsets of dendritic cells in the lungs of CCR6(-/-) mice after allergen challenge. Using in vitro cell mixing studies with isolated pulmonary CD4(+) T cells and CD11c(+) cells from CCR6(+/+) or CCR6(-/-) mice, we demonstrate alterations in both CCR6(-/-) T cells and CCR6(-/-) pulmonary APCs to elicit IL-5 responses. Altogether, the defect in CCR6(-/-) mice appears to be primarily due to an alteration in T cell activation, but also appears to include local pulmonary APC defects.