Article abstract


Nature Immunology 10, 66 - 74 (2008)
Published online: 23 November 2008 | doi:10.1038/ni.1668

Human fetal lymphoid tissue–inducer cells are interleukin 17–producing precursors to RORC+ CD127+ natural killer–like cells

Tom Cupedo1,2, Natasha K Crellin3, Natalie Papazian1, Elwin J Rombouts1, Kees Weijer2, Jane L Grogan3, Willem E Fibbe4, Jan J Cornelissen1 & Hergen Spits2,3


The human body contains over 500 individual lymph nodes, yet the biology of their formation is poorly understood. Here we identify human lymphoid tissue–inducer cells (LTi cells) as lineage-negative RORC+ CD127+ cells with the functional ability to interact with mesenchymal cells through lymphotoxin and tumor necrosis factor. Human LTi cells were committed natural killer (NK) cell precursors that produced interleukin 17 (IL-17) and IL-22. In vitro, LTi cells gave rise to RORC+ CD127+ NK cells that retained the ability to produce IL-17 and IL-22. Postnatally, similar populations of LTi cell–like cells and RORC+ CD127+ NK cells were present in tonsils, and both secreted IL-17 and IL-22 but no interferon-gamma. Our data indicate that lymph node organogenesis is controlled by an NK cell precursor population with adaptive immune features and demonstrate a previously unappreciated link between the innate and adaptive immune systems.

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  1. Department of Hematology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
  2. Department Cell Biology and Histology, Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
  3. Department of Immunology, Genentech Inc., South San Francisco, California 94080, USA.
  4. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.

Correspondence to: Tom Cupedo1,2 e-mail: t.cupedo@erasmusmc.nl




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