TH2 CELLS MEDIATE IL-4-DEPENDENT LOCAL TISSUE INFLAMMATION

We investigated whether polyclonal murine Th1 and Th2 cells obtained a fter short term culture in vitro were capable of mediating tissue infl ammation in vivo. Th cells were pulsed with mAb to the TCR/CD3 complex and injected into the footpads or ears of naive syngeneic recipient m ice. Th1 induced delayed swelling that peaked at 24 to 48 h and lasted greater-than-or-equal-to 5 days. Th2-induced swelling peaked at 6 h a nd lasted less-than-or-equal-to 48 h. Similar responses were also obse rved in athymic nude mice. Lesions with both Th1 and Th2 cells contain ed a predominant neutrophilic infiltrate at 6 h, and mainly mononuclea r cells at 48 h. The inflammatory response with Th2 was blocked by cyc losporin A, by mAb to IL-4 or by soluble rIL-4R. The requirement for I L-4 was early and transient. Four alloreactive short term Th2 clones i nduced swelling in allogeneic recipients. mAb- and IL-4-dependent swel ling responses were also observed with two long term Th2 clones. Our r esults demonstrate that Th2 cells mediate IL-4-dependent tissue inflam mation, and strengthen the concept that Th2 cells play an important ro le in some T cell-dependent immune reactions and, possibly, in allergi c disorders such as atopic dermatitis and allergic asthma.