Sustained signaling by canonical T helper cytokines throughout the reactive lymph node

Cytokines are soluble proteins that regulate immune responses. A current paradigm is that cytokine production in lymphoid tissues is tightly localized and signaling occurs between conjugate cells. Here we assess cytokine signaling during infection by measuring in vivo phosphorylation of intracellular signal transducers and activators of transcription (STATs). We show that interferon γ (IFN-γ) and interleukin 4 (IL-4) signal to the majority of lymphocytes throughout the reactive lymph node, and that IL-4 conditioning of naïve, bystander cells is sufficient to override opposing Th1 instruction. Our results demonstrate that, despite localized production, cytokines can permeate a lymph node and modify the majority of cells therein. Cytokine conditioning of bystander cells could provide a mechanism by which chronic worm infections subvert the host response to subsequent infections or vaccination attempts.