title: Both stat5a and stat5b are required for antigen-induced eosinophil and T-cell recruitment into the tissue.
abstract: 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 diminished 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 diminished in Stat5a(-/- )mice and Stat5b(-/-) mice, suggesting that the generation of antigen-primed T cells may be compromised in Stat5a(-/-) mice and Stat5b(-/-) mice and this defect may account for the diminished antigen-induced T-cell infiltration into the airways. Interestingly, IL-4 and IL-5 production from anti-CD3-stimulated splenocytes was diminished in Stat5a(-/-) mice and Stat5b(-/-) mice. However, antigen-specific IgE and IgG1 production was diminished in Stat5a(-/-) mice but not in Stat5b(-/-) mice, whereas antigen-specific IgG2a production was increased in Stat5a(-/-) mice, suggesting the enhanced Th1 responses in Stat5a(-/-) mice. Finally, we found that eosinophilopoiesis induced by the administration of recombinant IL-5 was also diminished in Stat5a(-/-) mice and Stat5b(-/-) mice. Together, these results indicate that both Stat5a and Stat5b are essential for induction of antigen-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 diminished IL-5 responsiveness of eosinophils. (Blood. 2000;95:1370-1377)
authors.affiliation: Department of Internal Medicine II, Chiba University School of Medicine, Chiba, Japan.
authors.forename: S i
authors.initials: Si
authors.lastname: Kagami
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Kumano
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Suto
authors.forename: K
authors.initials: K
authors.lastname: Imada
authors.forename: H W
authors.initials: HW
authors.lastname: Davey
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Takatsu
authors.forename: W J
authors.initials: WJ
authors.lastname: Leonard
authors.forename: I
authors.initials: I
authors.lastname: Iwamoto
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001854:Bone Marrow Cells / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004804:Eosinophils / Q000276:immunology*; D006410:Hematopoiesis / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D015848:Interleukin-5 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008894:Milk Proteins; D010047:Ovalbumin / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology*; D050799:STAT5 Transcription Factor; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D015848:Interleukin-5; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D015534:Trans-Activators; D007073:Immunoglobulin E; D010047:Ovalbumin