T regulatory cells control numbers of NK cells and CD8α+ immature dendritic cells in the lymph node paracortex

The spleen contains numerous NK cells whose differentiation profile is characterized by a preponderance of mature elements located mainly in the red pulp. In contrast, lymph nodes (LNs) contain few NK cells and they are sited mostly in T cell zones and skewed toward immature developmental stages. We show that, in mice, naturally occurring CD4(+)Foxp3(+) regulatory T (Treg) cells are both necessary and sufficient to repress accumulation of NK cells in resting LNs. Moreover, we present evidence that Treg cells hamper generation of mature NK cells through short-range interactions with NK precursors. In turn, mature NK cells specifically regulate the amount of CD8 alpha(+) phenotypically immature dendritic cells present in LN T cell zones. We propose that the dominant influence of Treg cells on NK cell precursors and CD8 alpha(+) immature dendritic cells explains why quiescent LNs in the absence of infection function as privileged sites for induction and maintenance of tolerance to peripheral Ags.