The Abundant NK Cells in Human Secondary Lymphoid Tissues Require Activation to Express Killer Cell Ig-Like Receptors and Become Cytolytic

Guido Ferlazzo*, Dolca Thomas, Shao Lee Lin, Kiera Goodman, Barbara Morandi, William A. Muller, Alessandro Moretta, Christian Münz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

440 Scopus citations

Abstract

Natural killer cells are important cytolytic cells in innate immunity. We have characterized human NK cells of spleen, lymph nodes, and tonsils. More than 95% of peripheral blood and 85% of spleen NK cells are CD56 dimCD16+ and express perforin, the natural cytotoxicity receptors (NCRs) NKp30 and NKp46, as well as in part killer cell Ig-like receptors (KIRs). In contrast, NK cells in lymph nodes have mainly a CD56 brightCD16- phenotype and lack perforin. In addition, they lack KIRs and all NCR expression, except low levels of NKp46. The NK cells of tonsils also lack perforin, KIRs, NKp30, and CD16, but partially express NKp44 and NKp46. Upon IL-2 stimulation, however, lymph node and tonsilar NK cells up-regulate NCRs, express perforin, and acquire cytolytic activity for NK-sensitive target cells. In addition, they express CD16 and KIRs upon IL-2 activation, and therefore display a phenotype similar to peripheral blood NK cells. We hypothesize that IL-2 can mobilize the NK cells of secondary lymphoid tissues to mediate natural killing during immune responses. Because lymph nodes harbor 40% and peripheral blood only 2% of all lymphocytes in humans, this newly characterized perforin- NK cell compartment in lymph nodes and related tissues probably outnumbers perforin+ NK cells. These results also suggest secondary lymphoid organs as a possible site of NK cell differentiation and self-tolerance acquisition.

Original languageEnglish (US)
Pages (from-to)1455-1462
Number of pages8
JournalJournal of Immunology
Volume172
Issue number3
DOIs
StatePublished - Feb 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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