title: Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells.
abstract: The current paradigm surrounding allergen-mediated T helper type 2 (Th2) immune responses in the lung suggests an almost hegemonic role for T cells. Our studies propose an alternative hypothesis implicating eosinophils in the regulation of pulmonary T cell responses. In particular, ovalbumin (OVA)-sensitized/challenged mice devoid of eosinophils (the transgenic line PHIL) have reduced airway levels of Th2 cytokines relative to the OVA-treated wild type that correlated with a reduced ability to recruit effector T cells to the lung. Adoptive transfer of Th2-polarized OVA-specific transgenic T cells (OT-II) alone into OVA-challenged PHIL recipient mice failed to restore Th2 cytokines, airway histopathologies, and, most importantly, the recruitment of pulmonary effector T cells. In contrast, the combined transfer of OT-II cells and eosinophils into PHIL mice resulted in the accumulation of effector T cells and a concomitant increase in both airway Th2 immune responses and histopathologies. Moreover, we show that eosinophils elicit the expression of the Th2 chemokines thymus- and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in the lung after allergen challenge, and blockade of these chemokines inhibited the recruitment of effector T cells. In summary, the data suggest that pulmonary eosinophils are required for the localized recruitment of effector T cells.
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Jacobsen
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Ochkur
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Pero
authors.forename: Anna G
authors.initials: AG
authors.lastname: Taranova
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Protheroe
authors.forename: Dana C
authors.initials: DC
authors.lastname: Colbert
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D054414:Chemokine CCL17 / Q000096:biosynthesis; D054422:Chemokine CCL22 / Q000096:biosynthesis; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D000485:Allergens; C499538:Ccl17 protein, mouse; C515483:Ccl22 protein, mouse; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D010047:Ovalbumin