Characterization and IL-15 dependence of NK cells in humanized mice.
Natural Killer cells can distinguish between healthy and malignant cells and have the unique ability to lyse tumour cells without prior sensitization. Differences between murine and human NK cells complicate the translation of this knowledge into useful therapeutics. Humanized mouse models that support the development of human leukocytes are a promising avenue of research that aims to address this problem. Here we provide an in-depth phenotypic analysis of human NK cells in Balb/c Rag2(-/-)γ(c)(-/-) mice reconstituted with human hematopoietic stem cells. We have examined the development of NK cells in bone marrow, thymous, spleen, lymph node (LN) and liver. Interestingly, in naive reconstituted mice, NK cells were found in thymus and LN, but not in bone marrow. These NK cells expressed several inhibitory and activating receptors needed for malignant cell detection. Furthermore, we confirm that administration of recombinant human interleukin-15 (rhIL-15) or Ad-vector expressing hIL-15 is able to significantly enhance NK cell development and maturation, particularly in bone marrow and liver, in this model. Our results suggest that human NK cells developed in mice may have phenotypes and tissue distributions similar to those seen in human.
Pek
Elisabeth A
EA
Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Chan
Tiffany
T
Reid
Sarah
S
Ashkar
Ali A
AA
D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D023421:Models, Animal; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013045:Species Specificity
D004268:DNA-Binding Proteins; D007127:Immunoglobulin Constant Regions; D019409:Interleukin-15; C499308:Rag2 protein, mouse; D011994:Recombinant Proteins