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+ Immature Dendritic Cells in the Lymph Node Paracortex1
,
* Institute of Research in Immunology and Cancer and
Department of Medicine, University of Montreal, Montreal, Quebec, Canada;
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada; and
Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada
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
+ 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+ 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Canadian Institutes for Health Research (CIHR) to C.A.P. (MOP 67211) and C.P. (MOP 42384). M.G. and J.S.-P. were supported by the Cole Foundation and the CIHR, respectively. E.Y. is a recipient of a fellowship from the CIHR Training Grant in Neuroinflammation. C.A.P. and C.P. hold Canada Research Chairs in "Regulatory Lymphocytes of the Immune System" and "Immunobiology," respectively.
2 Address correspondence and reprint requests to Dr. Claude Perreault, Institute of Research in Immunology and Cancer, University of Montreal, Casier postal 6128, succ. Centre-ville, Montréal, Quebec, Canada. E-mail address: c.perreault{at}videotron.ca
3 Abbreviations used in this paper: BM, bone marrow; DC, dendritic cell; iDC, immature DC; LN, lymph node; Treg, regulatory T; SCF, stem cell factor.
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