ANTI-IL-4 DIMINISHES INVIVO PRIMING FOR ANTIGEN-SPECIFIC IL-4 PRODUCTION BY T-CELLS

Treatment of mice with neutralizing monoclonal anti-IL-4 antibodies at the time of immunization with keyhole limpet hemocyanin causes significant inhibition of priming of T cells for the production of IL-4 upon subsequent in vitro challenge. BALB/c mice received a single injection of anti-IL-4 at the time of immunization. T cells purified from spleen and lymph nodes were obtained at 6 to 7 days and at 30 to 75 days after priming. In the 6- to 7-day group, IL-4 production in response to keyhole limpet hemocyanin among the recipients of anti-IL-4 was reduced by more than twofold in four of four experiments, when low density T cells were challenged. In some, but not all, of these experiments, production of IFN-gamma was enhanced at least twofold. Measurement of frequency of IL-4-producing, keyhole limpet hemocyanin-specific T cells indicated a twofold reduction in the anti-IL-4-treated mice. Among cells obtained between 30 and 75 days after priming, production of IL-4 was diminished in four of four cases in high density cells and three of four cases in low density cells. T cells were also prepared from mice that received a secondary in vivo challenge 90 to 105 days after priming. T cells from boosted donors that had received a single injection of anti-IL-4 at the time of priming showed diminished production of IL-4 in each experiment. By contrast, treatment with anti-IL-4 at the time of secondary challenge did not diminish IL-4-producing capacity of cells from mice that were primed in the absence of anti-IL-4. These results indicate that IL-4 is important in vivo in priming T cells to develop into IL-4-producing cells and indicate an important physiologic role for IL-4 in the establishment of lymphokine-producing phenotype.