| First Author | Strowig T | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 20 | Pages | 4158-67 |
| PubMed ID | 20671122 | Mgi Jnum | J:167434 |
| Mgi Id | MGI:4868286 | Doi | 10.1182/blood-2010-02-270678 |
| Citation | Strowig T, et al. (2010) Human NK cells of mice with reconstituted human immune system components require preactivation to acquire functional competence. Blood 116(20):4158-67 |
| abstractText | 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 IL2Rgamma(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-gamma 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. |
