title: Interleukin-5-producing CD4+ T cells play a pivotal role in aeroallergen-induced eosinophilia, bronchial hyperreactivity, and lung damage in mice.
abstract: Although activated CD4+ T cells have been implicated in the pathogenesis of asthma, the direct contribution of this leukocyte to the induction of aeroallergen-induced bronchial hyperreactivity and lung damage is unknown. In the present investigation, we have used a model of allergic airways inflammation, which displays certain phenotypic characteristics of late-phase asthmatic responses, together with interleukin-5-deficient (IL-5-/- ) mice and donor antigen-specific CD4+ TH2-type cells to obtain unequivocal evidence for a role of this T lymphocyte in the pathophysiology of allergic airways inflammation. Antigen-primed CD4+ T cells and CD4- cells (CD4+-depleted population) were purified from the spleens of ovalbumin (OVA)-sensitized wild-type mice and adoptively transferred to OVA-sensitized and nonsensitized IL-5-/- mice. In vitro stimulation of the purified cell populations with OVA resulted in the secretion of IL-4 and IL-5, but not interferon-gamma, from the CD4+ T cells, indicating that they were of the TH2 type. In contrast, interferon-gamma, but not IL-4 and IL-5, was produced by the CD4- T cells. The CD4+ TH2-type cells (but not the CD4 cells) reconstituted aeroallergen (OVA)-induced blood and airways eosinophilia, lung damage, and airways hyperreactivity to 1-methacholine in IL-5-/- mice. The reconstitution did not require prior sensitization of the mice, but it did not occur if they were aerosolized with saline instead of OVA. The circulating levels of OVA-specific -IgE and -IgG1 were not significantly altered by the adoptive transfer of either cell population. These investigations establish that IL-5-secreting CD4+ TH2-type cells play a pivotal role in generating blood and airways eosinophilia and in the subsequent development of bronchial hyperreactivity and lung damage that occurs in response to aeroallergens.
authors.affiliation: Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT.
authors.forename: S P
authors.initials: SP
authors.lastname: Hogan
authors.forename: A
authors.initials: A
authors.lastname: Koskinen
authors.forename: K I
authors.initials: KI
authors.lastname: Matthaei
authors.forename: I G
authors.initials: IG
authors.lastname: Young
authors.forename: P S
authors.initials: PS
authors.lastname: Foster
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D001249:Asthma / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology*; D007249:Inflammation; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000009:adverse effects*
chemical_list: D000485:Allergens; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin