IL-6 directs the differentiation of IL-4-producing CD4+ T cells. This study shows that IL-6, secreted by antigen-presenting cells (APCs), can polarize naive CD4+ T cells into Th2 effector cells by inducing IL-4 production. IL-6 also antagonizes IL-12-mediated Th1 differentiation. The study demonstrates that the cytokine environment, particularly IL-6 or IL-12, determines the Th1 or Th2 immune response. IL-4 is the most potent factor for Th2 differentiation, while IL-12 drives Th1 differentiation. The source of initial polarizing cytokines remains unclear, but IL-6 is shown to be a key factor in Th2 polarization. IL-6 acts directly on T cells to promote Th2 differentiation by upregulating IL-4 gene expression. In vitro experiments show that IL-6 is required for Th2 differentiation, and its absence impairs Th2 responses. IL-6-deficient mice exhibit impaired immune responses, highlighting the importance of IL-6 in Th2 polarization. The study provides evidence that IL-6 is a critical factor in the choice between Th1 and Th2 immune responses.IL-6 directs the differentiation of IL-4-producing CD4+ T cells. This study shows that IL-6, secreted by antigen-presenting cells (APCs), can polarize naive CD4+ T cells into Th2 effector cells by inducing IL-4 production. IL-6 also antagonizes IL-12-mediated Th1 differentiation. The study demonstrates that the cytokine environment, particularly IL-6 or IL-12, determines the Th1 or Th2 immune response. IL-4 is the most potent factor for Th2 differentiation, while IL-12 drives Th1 differentiation. The source of initial polarizing cytokines remains unclear, but IL-6 is shown to be a key factor in Th2 polarization. IL-6 acts directly on T cells to promote Th2 differentiation by upregulating IL-4 gene expression. In vitro experiments show that IL-6 is required for Th2 differentiation, and its absence impairs Th2 responses. IL-6-deficient mice exhibit impaired immune responses, highlighting the importance of IL-6 in Th2 polarization. The study provides evidence that IL-6 is a critical factor in the choice between Th1 and Th2 immune responses.