Augmentation of LTC4 synthesis in human eosinophils caused by CD3-stimulated Th2-like cells in vitro

We assessed the effect of anti-CD3-stimulated secretion of cultured human T h1- and Th2-like cells on leukotriene C-4 (LTC4) secretion in isolated huma n eosinophils. T helper (Th) cell subsets were generated from human naive C D4(+) T cells cocultured with irradiated human transformed B cells and eith er recombinant human interleukin (rhIL)-1 beta plus rhIL-6 plus rhIL-12 for Th1-like cells or rhIL-1 beta plus rhIL-6 plus rhIL-4 for Th2-like cells. Coincubation of eosinophils with 1:5 dilution of Th2-supernatant (Sup) caus ed an increase in LTC4 secretion caused by 0.1 mu M formyl-Met-Leu-Phe and 5 mu g/ml cytochalasin B from 921 +/- 238 to 3,067 +/- 1,462 pg/10(6) eosin ophils (P < 0.01). Th1-Sup at the same dilution had no augmenting effect on stimulated secretion of LTC4 in eosinophils despite substantial concentrat ions of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the su pernatant. Dilution of Th1- Sup caused increased LTC4 that returned to base line after immunoabsorption of GM-CSF, suggesting the presence of a possibl e inhibitory factor. We demonstrate that pretreatment of eosinophils with 1 :5 dilution of Th2-Sup but not of Th1-Sup causes substantial augmentation o f LTC4 secretion in vitro and establishes that human Th2 cells cause direct augmentation of LTC4 secretion within 15-30 min of exposure.