Both Stat5a and Stat5b are required for antigen-induced eosinophil and T-cell recruitment into the tissue

Antigen-induced eosinophil recruitment into the airways of sensitized mice is mediated by CD4(+) T cells and their cytokines, especially IL-5. In this study, we found that the antigen-induced airway eosinophilia was diminishe d in Stat5a-deficient (Stat5a(-/-)) mice and Stat5b-deficient (Stat5b(-/-)) mice. We also found that antigen-induced CD4(+) T-cell infiltration and IL -5 production in the airways were diminished in Stat5a(-/-) mice and Stat5b (-/-) mice. Moreover, antigen-induced proliferation of splenocytes was dimi nished in Stat5a(-/-) mice and Stat5b(-/-) mice, suggesting that the genera tion of antigen-primed T cells may be compromised in Stat5a(-/-) mice and S tat5b(-/-) mice and this defect may account for the diminished antigen indu ced T-cell infiltration into the airways. Interestingly, IL-4 and IL-5 prod uction from anti-CD3-stimulated splenocytes was diminished in Stat5a(-/-) m ice and Stat5b(-/-) mice. However, antigen-specific IgE and IgG1 production was diminished in Stat5a(-/-) mice but not in Stat5b(-/-) mice, whereas an tigen-specific IgG2a production was increased in Stat5a(-/-) mice, suggesti ng the enhanced Th1 responses in Stat5a(-/-) mice. Finally, we found that e osinophilo-poiesis induced by the administration of recombinant IL-5 was al so diminished in Stat5a(-/-) mice and Stat5b(-/-) mice. Together, these res ults indicate that both Stat5a and Stat5b are essential for induction of an tigen-induced eosinophil recruitment into the airways and that the defects in antigen-induced eosinophil recruitment in Stat5a(-/-) mice and Stat5b(-/ -) mice result from both impaired IL-5 production in the airways and dimini shed IL-5 responsiveness of eosinophils. (C) 2000 by The American Society o f Hematology.