Dynamic Roles for IL-2-STAT5 Signaling in Effector and Regulatory CD4⁺ T Cell Populations

CD4⁺ Th cells are responsible for orchestrating diverse, pathogen-specific immune responses through their differentiation into a number of subsets, including T_H1, T_H2, T_H9, T follicular helper, T follicular regulatory, and regulatory T cells. The differentiation of each subset is guided by distinct regulatory requirements, including those derived from extracellular cytokine signals. IL-2 has emerged as a critical immunomodulatory cytokine that both positively and negatively affects the differentiation of individual Th cell subsets. IL-2 signals are propagated, in part, via activation of STAT5, which functions as a key regulator of CD4⁺ T cell gene programs. In this review, we discuss current understanding of the mechanisms that allow IL-2-STAT5 signaling to exert divergent effects across CD4⁺ T cell subsets and highlight specific roles for this pathway in the regulation of individual Th cell differentiation programs.