Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses.
Using a single vector targeting strategy, we have generated mice with a combined deficiency of interleukin (IL)-4 and IL-13 to clarify their roles in T helper type 2 (Th2) cell responses. Using immunological challenges normally characterized by a Th2-like response, we have compared the responses of the double-deficient mice with those generated by wild-type, IL-4-deficient, and IL-13-deficient mice. Using a pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that although eosinophil infiltration, immunoglobulin E, and IL-5 production are reduced in the IL-4-deficient mice and IL-13-deficient mice, they are abolished only in the combined absence of both cytokines. Furthermore, IL-4/13-deficient animals are severely impaired in their ability to expel the gastrointestinal nematode Nippostrongylus brasiliensis. Unexpectedly, N. brasiliensis-infected IL-4/13-deficient mice developed elevated IL-5 and eosinophilia, indicating that compensatory mechanisms exist for the expression of IL-5, although serum IgE remained undetectable. IL-4/13-deficient mice default to a Th1-like phenotype characterized by the expression of interferon gamma and the production of IgG2a and IgG2b. We conclude that IL-4 and IL-13 cooperate to initiate rapid Th2 cell-driven responses, and that although their functions overlap, they perform additive roles.
D000818:Animals; D004802:Eosinophilia / Q000209:etiology; D006099:Granuloma / Q000209:etiology / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018793:Interleukin-13 / Q000172:deficiency* / Q000276:immunology; D015847:Interleukin-4 / Q000172:deficiency* / Q000276:immunology; D015848:Interleukin-5 / Q000378:metabolism; D008171:Lung Diseases / Q000209:etiology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009559:Nippostrongylus; D010047:Ovalbumin / Q000276:immunology; D012550:Schistosoma mansoni; D017206:Strongylida Infections / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*