Human NK cells of mice with reconstituted human immune system components require preactivation to acquire functional competence

Till Strowig, Obinna Chijioke, Paolo Carrega, Frida Arrey, Sonja Meixlsperger, Patrick C. Rämer, Guido Ferlazzo, Christian Münz

Research output: Contribution to journalArticle

Abstract

To investigate human natural killer (NK) - cell reactivity in vivo we have reconstituted human immune system components by transplantation of human hematopoietic progenitor cells into NOD-scid IL2Rγnull mice. We demonstrate here that this model allows the development of all NK-cell subsets that are also found in human adult peripheral and cord blood, including NKp46+CD56- NK cells. Similar to human cord blood, NK cells from these reconstituted mice require preactivation by interleukin-15 to reach the functional competence of human adult NK cells. Mainly the terminally differentiated CD16+ NK cells demonstrate lower reactivity without this stimulation. After preactivation, both CD16+ and CD16 - NK cells efficiently produce interferon-γ and degranulate in response to stimulation with NK cell - susceptible targets, including K562 erythroleukemia cells. NK-cell lines, established from reconstituted mice, demonstrate cytotoxicity against this tumor cell line. Importantly, preactivation can as well be achieved by bystander cell maturation via poly I:C stimulation in vitro and injection of this maturation stimulus in vivo. Preactivation in vivo enhances killing of human leukocyte antigen class I negative tumor cells after their adoptive transfer. These data suggest that a functional, but resting, NK-cell compartment can be established in immune-compromised mice after human hematopoietic progenitor cell transfer.

Original languageEnglish
Pages (from-to)4158-4167
Number of pages10
JournalBlood
Volume116
Issue number20
DOIs
Publication statusPublished - Nov 18 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Strowig, T., Chijioke, O., Carrega, P., Arrey, F., Meixlsperger, S., Rämer, P. C., Ferlazzo, G., & Münz, C. (2010). Human NK cells of mice with reconstituted human immune system components require preactivation to acquire functional competence. Blood, 116(20), 4158-4167. https://doi.org/10.1182/blood-2010-02-270678