INTERLEUKIN-5-PRODUCING CD4(-CELLS PLAY A PIVOTAL ROLE IN AEROALLERGEN-INDUCED EOSINOPHILIA, BRONCHIAL HYPERREACTIVITY, AND LUNG DAMAGE IN MICE() T)

Although activated CD4(+) T cells have been implicated in the pathogen esis of asthma, the direct contribution of this leukocyte to the induc tion of aeroallergen-induced bronchial hyperreactivity and lung damage is unknown. In the present investigation, we have used a model of all ergic airways inflammation, which displays certain phenotypic characte ristics 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-prime d CD4(+) T cells and CD4(-) cells (CD4(+)-depleted population) were pu rified from the spleens of ovalbumin (OVA)-sensitized wild-type mice a nd 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. I n contrast, interferon-gamma, but not IL-4 and IL-5, was produced by t he CD4(-) T cells. The CD4(+) TH2-type cells (but not the CD4(-) cells ) reconstituted aeroallergen (OVA)-induced blood and airways eosinophi lia, lung damage, and airways hyperreactivity to beta-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 salin e instead of OVA. The circulating levels of OVA-specific-IgE and -IgG( 1) were not significantly altered by the adoptive transfer of either c ell 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 hyperreac tivity and lung damage that occurs in response to aeroallergens.