AbstractThe lack of cell‐mediated (Thl‐like) immunity that is often associated with strong humoral immune responses is thought to be due in part to the inhibition of Thl effector function by the Th2‐derived cytokine interleukin‐10 (IL‐10). This hypothesis, however, is based entirely on results fromin vitrostudies, wherein IL‐10 has been shown to inhibit Thl cytokine synthesis. In this study we have compared the regulatory effects of both IL‐4 and IL‐10 on the development of a more complex Thl effector functionin vivo, the development of delayed‐type hypersensitivity (DTH) toLeishmania majorin mice immune toLeishmania.The results revealed two findings unexpected fromin vitrostudies with Thl clones. First, optimal inhibition of the DTH response (up to 70 ), assessed by footpad swelling and leukocytic infiltration, required the combination of IL‐4 and IL‐10, indicating that these two activities synergized to inhibit DTH reactivity. Second, IL‐4 inhibited interferon‐γ (IFN‐γ) production by lymph node cells draining the site of antigen challenge as well as did IL‐10. The combination of both cytokines was no more effective than either alone. The mechanism by which IL‐4 and IL‐10 acted to inhibit DTH responses did not appear to be through inhibition of IFN‐γ or tumor necrosis factor production as treatment with antibodies which neutralized these activities failed to inhibit DTH responses. Inhibition of the DTH with IL‐4 and IL‐10 is the most effective specific regulator of DTH responses reported and the only one capable of modulating tuberculin DTH. These data establish IL‐4 and IL‐10 as potent inhibitors of Thl effector functionin vivoand suggest their utility in controlling deleterious Thl‐mediated inflammatory responses such as
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