Interleukin (IL)-6 is identified as a key cytokine that polarizes naive CD4+ T cells to effector Th2 cells by inducing the initial production of IL-4. This process is independent of antigen-presenting cells (APCs) and involves direct action on T cells. IL-6 also antagonizes the differentiation of Th1 cells, suggesting that it plays a crucial role in the choice between Th1 and Th2 immune responses. The study provides evidence that IL-6 is a critical factor in the initial production of IL-4, which is essential for the polarization of Th2 cells. In vivo experiments in IL-6-deficient mice further support the role of IL-6 in Th2 cell differentiation, highlighting its importance in immune responses to various pathogens.Interleukin (IL)-6 is identified as a key cytokine that polarizes naive CD4+ T cells to effector Th2 cells by inducing the initial production of IL-4. This process is independent of antigen-presenting cells (APCs) and involves direct action on T cells. IL-6 also antagonizes the differentiation of Th1 cells, suggesting that it plays a crucial role in the choice between Th1 and Th2 immune responses. The study provides evidence that IL-6 is a critical factor in the initial production of IL-4, which is essential for the polarization of Th2 cells. In vivo experiments in IL-6-deficient mice further support the role of IL-6 in Th2 cell differentiation, highlighting its importance in immune responses to various pathogens.