Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-44301
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.
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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 IL2Rγ(null) 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.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Experimental Immunology|
|DDC:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||03 Feb 2011 09:46|
|Last Modified:||01 Dec 2013 09:19|
|Publisher:||American Society of Hematology|
|Additional Information:||This research was originally published in Blood. 2010 Nov 18;116(20):4158-67. Copyright by the American Society of Hematology|
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