Interacting positive and negative feedback loops promote and control chronic activation in HIV-1–infected lymph nodes. T cells are specifically activated by HIV and other microbial antigens, and nonspecifically, as bystanders, by cytokines and other factors associated with inflammation, including Toll-like receptor (TLR) agonists. Such activation leads to proliferation, differentiation, and cytokine secretion; the latter contribute to inflammation and bystander activation (positive feedback). Different effector cells secrete inhibitory cytokines and apoptosis-inducing factors that may affect T cells and dendritic cells (negative feedback). Also depicted are ongoing cycles of infection that connect to both feedback loops.

Interacting positive and negative feedback loops promote and control chronic activation in HIV-1–infected lymph nodes. T cells are specifically activated by HIV and other microbial antigens, and nonspecifically, as bystanders, by cytokines and other factors associated with inflammation, including Toll-like receptor (TLR) agonists. Such activation leads to proliferation, differentiation, and cytokine secretion; the latter contribute to inflammation and bystander activation (positive feedback). Different effector cells secrete inhibitory cytokines and apoptosis-inducing factors that may affect T cells and dendritic cells (negative feedback). Also depicted are ongoing cycles of infection that connect to both feedback loops.

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