T Regulatory Cells Control the Numbers of NK Cells and Thereby Protect CD8alpha+ Immature Dendritic Cells Presence in the Lymph Node Paracortex (88.13)

Abstract

Abstract In the absence of infection, the spleen contains numerous natural killer (NK) cells located mainly in the red pulp and whose differentiation profile is characterized by a preponderance of mature elements. In contrast, lymph nodes (LNs) contain few NK cells that are sited mostly in T-cell zones and that are phenotypically skewed toward immature developmental stages. We present evidence that CD4+CD25+ T regulatory (Treg) cells hamper generation of mature NK cells in the LNs through short-range interactions with NK precursors. Moreover, we show that Treg cells are both necessary and sufficient to repress accumulation of NK cells in resting LNs and an absence of Treg totally alleviates the differentiation blockade and leads to an accumulation of mature NK cells in the LN paracortex. In turn, mature NK cells specifically regulate the amount of CD8α+ phenotypically immature dendritic cells (iDCs) present in LN T-cell zones. We propose that the dominant influence of Treg cells on NK cell precursors and consequently on CD8α+ iDCs explains why “quiescent” LNs, in the absence of infection, function as privileged sites for induction and maintenance of tolerance to peripheral self antigens.