SP Hogan, A Koskinen, KI Matthaei, IG Young and PS Foster
Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT.

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.

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