Perspective studies. Whereas investigations in humans highlight an association of Th2 cells and asthma, animal studies show cause and effect. Many studies have shown that eosinophilic airway inflammation and AHR are dependent upon CD4+ T cells (1, 12). In addition, adoptive transfer of CD4+ T cells from animals with antigeninduced AHR resulted in airway inflammation and hyperresponsiveness in aerosol-challenged recipient mice (20). The ability of Th2 cells to stimulate the characteristic features of asthma was recently shown. When antigen-specific Th1 or Th2 cells were generated in vitro, transferred into recipient mice, and activated in the respiratory tract with inhaled antigen, Th2 cells induced airway eosinophilia, mucus hypersecretion, and AHR (2, 21). Th1 cells resulted in a neutrophil-predominant inflammatory response without any of the characteristic features of asthma. Thus, Th2 cells can activate inflammatory pathways that result in airway inflammation and AHR after short-term exposure to antigen. Constitutive production of individual Th2 cytokines has also been found to induce an asthma-like syndrome. Transgenic mice that overexpress the Th2 cytokines—IL-4, IL-5, IL-13, and IL-9—in the airway epithelium exhibit common inflammatory features in the airways, including eosinophilia and mucus overproduction. Transgenic mice that overexpress IL-13, IL-9, and IL-5 showed AHR and collagen deposition in the airways, indicating that chronic exposure to Th2 cytokines can also induce airway remodeling (see article by Elias et al. in this series). Therefore, it appears that activation of Th2 cells is sufficient for the induction of inflammation and the chronic pathologic changes associated with asthma. Animal studies have now demonstrated how individual Th2 cytokines control different features of the inflammatory response in asthma. IL-5 production is essential for airway eosinophilia (12), and, in some cases, AHR depends on eosinophilia (1). Recent studies have shown that the induction of AHR, eosinophilia, and mucus production by Th2 cells requires signaling through IL-4R (1). This appears predominantly to reflect the role of IL-13 in these processes (22, 23), because in the absence of IL-4, AHR, lung eosinophilia, and mucus production can still be induced (2, 21). Whether IL-4 can also stimulate these asthmatic phenomena in the absence of IL-13 has not yet been shown. IL-4 is critical for Th2 cell induction, and IL-4 may be required for the persistence of Th2 cells in vivo in the lung (24). Th2 cytokines can induce a constellation of pathophysiologic changes in animals that resemble human asthma. But, the production of IL-4, IL-5, and IL-13 is not exclusive to CD4+ T cells. In fact, CD8+ and γ/δ T cells, and eosinophils, mast cells, and basophils have all been shown to produce these cytokines. Of all of these inflammatory cells, CD4+ T cells are typically present in higher numbers in the respiratory tract, thus explaining why the pathophysiologic abnormalities depend on CD4+ T cells in many animal models of asthma. But, in certain animal systems, eosinophils, mast cells, and CD8 or γ/δ T cells have been shown to contribute to airway inflammation and AHR (25, 26). Different animal strains or variations in methods for induction of airway inflammation may accentuate the effects of one cell type or another. Thus, these divergent results may indicate that the consequences of inflammation in a particular animal model depend on a non-CD4+ T cell that is contributing Th2 cytokines. What appears to be clear at present is that the secretion of Th2 cytokines is critical for the induction of the characteristic airway inflammation in animal models of asthma …