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 CB4⁺ 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.