20962093
not annotated - annotated - LINNAEUS only
Human pluripotent stem cells produce natural killer cells that mediate anti-HIV-1 activity by utilizing diverse cellular mechanisms.
Cell-based therapies against HIV/AIDS have been gaining increased interest. Natural killer (NK) cells are a key component of the innate immune system with the ability to kill diverse tumor cells and virus-infected cells. While NK cells have been shown to play an important role in the control of HIV-1 replication, their functional activities are often compromised in HIV-1-infected individuals. We have previously demonstrated the derivation of NK cells from human embryonic stem cells (hESCs) with the ability to potently kill multiple types of tumor cells both in vitro and in vivo. We now demonstrate the derivation of functional NK cells from human induced pluripotent stem cells (iPSCs). More importantly, both hESC- and iPSC-derived NK cells are able to inhibit HIV-1 NL4-3 infection of CEM-GFP cells. Additional studies using HIV-1-infected human primary CD4(+) T cells illustrated that hESC- and iPSC-derived NK cells suppress HIV-1 infection by at least three distinct cellular mechanisms: killing of infected targets through direct lysis, antibody-dependent cellular cytotoxicity, and production of chemokines and cytokines. Our results establish the potential to utilize hESC- and iPSC-derived NK cells to better understand anti-HIV-1 immunity and provide a novel cellular immunotherapeutic approach to treat HIV/AIDS.
Ann file
T1 Species 0 5 Human
N1 Reference T1 Taxonomy:9606
T2 Out-of-scope 76 81 HIV-1
N2 Reference T2 Taxonomy:11676
T3 Species 431 436 HIV-1
N3 Reference T3 Taxonomy:11676
T4 Species 503 508 HIV-1
N4 Reference T4 Taxonomy:11676
T5 Species 595 600 human
N5 Reference T5 Taxonomy:9606
T6 Species 904 909 HIV-1
N6 Reference T6 Taxonomy:11676
T7 Species 969 974 HIV-1
N7 Reference T7 Taxonomy:11676
T8 Species 1071 1076 HIV-1
N8 Reference T8 Taxonomy:11676
T9 Out-of-scope 1376 1381 HIV-1
N9 Reference T9 Taxonomy:11676
T10 Species 783 788 human
T11 Species 984 989 human