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While the focus has been on the nerve-regenerative response, the effect of loss of innervation on lymph node function is unclear. Here, we show that the popliteal lymph node (popLN) receives direct neural input from the sciatic nerve and that sciatic denervation causes lymph node expansion. Loss of sympathetic, adrenergic tone induces the expression of IFN-\u03b3 in LN CD8 T cells, which is responsible for LN expansion. Surgery-induced IFN-\u03b3 expression and expansion can be rescued by \u03b22 adrenergic receptor agonists but not sensory nerve agonists. 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