The mechanisms regulating airway function are complex and still poorly understood. In diseases such as asthma, involvement of immune-dependent mechanisms has been suggested in causing changes in airway responsiveness to bronchoconstrictors. We now demonstrate that gammadelta T cells can regulate airway function in an alphabeta T cell-independent manner, identifying them as important cells in pulmonary homeostasis. This function of gammadelta T cells differs from previously described immune-dependent mechanisms and may reflect their interaction with innate systems of host defense.

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Cytokines play an important role in modulating inflammatory responses and, as a result, airway tone. IL-10 is a regulatory cytokine that has been suggested for treatment of asthma because of its immunosuppressive and anti-inflammatory properties. In contrast to these suggestions, we demonstrate in a model of allergic sensitization that mice deficient in IL-10 (IL-10؊͞؊) develop a pulmonary inflammatory response but fail to exhibit airway hyperresponsiveness in both in vitro and in vivo assessments of lung function. Reconstitution of these deficient mice with the IL-10 gene fully restores development of airway hyperresponsiveness comparable to control mice. These results identify an important role of IL-10, downstream of the inflammatory cascade, in regulating the tone of the airways after allergic sensitization and challenge. O ne of the basic characteristics of asthma is airway hyperresponsiveness (AHR), which increases after exposure to allergen. The level of responsiveness is demonstrated by showing increased responses to bronchoconstrictors such as methacholine (MCh). This heightened responsiveness is thought to result from a complex inflammatory cascade involving several cell types, including T lymphocytes and eosinophils (1, 2). T lymphocytes exert many of their effects by secreting an array of cytokines. In allergic asthma, type 2 T helper (Th) cell (Th2) cytokines dominate over Th1 cytokines and several studies suggest a critical role for IL-4, IL-5, and IL-13 in the development of AHR (3). The mechanisms underlying cytokinemediated influences on the tone of the airways are still largely unknown.IL-10 originally was described in mice as a factor inhibiting cytokine production from murine Th1 clones (4). Subsequent studies showed that IL-10 also can down-regulate Th2 clones and their production of IL-4 and IL-5 (5). In addition, IL-10 expresses a wide variety of effects on other immune cells, including stimulation of B cell differentiation and Ig secretion (6). The true biological effects of IL-10 have been difficult to delineate because the activities of this molecule on immune responsiveness vary considerably (7). However, it is known that adult mice deficient in IL-10 (IL-10Ϫ͞Ϫ) develop a CD4 T cell-dependent and IFN-␥-mediated enterocolitis (8).The data concerning the role of IL-10 in allergic inf lammation and AHR are contradictory. A few reports found reduced IL-10 mRNA expression both in peripheral blood mononuclear cells and bronchoalveolar lavage (BAL) lymphocytes of asthmatic patients (5) whereas others have demonstrated elevated levels in asthmatics (9 -11). Because of its immunosupressive properties in vitro and in animal models, IL-10 has been suggested as a potential therapy of allergic inf lammation and asthma (12).To define the role of IL-10 in controlling the development of allergic inflammation and AHR, we used an established mouse model of eosinophilic airway inflammation and allergen-driven alterations in airway function. Here, we describe that IL-10-deficient mice, sensitized and chal...