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- W1548811214 abstract "Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rare yet potentially fatal clinical syndrome caused by various congenital defects that result in defective perforin-dependent cytotoxicity of NK cells. This leads to increased T cell activation and proliferation and excessive cytokine production including IL-1, IL-6, IFN-γ, TNF-α and GM-CSF that causes sustained activation of macrophages that is manifest as extensive inflammation and tissue damage. One study showed that 50% of deaths from familial HLH were due to invasive fungal infections. We sought to investigate whether NK cells from a patient with HLH have defective anti-fungal activity and seek a potential therapeutic approach. NK cells (CD56+/CD3-) were isolated from a two-month-old boy with c1090-1091del of the perforin gene resulting in p.Leu364>Stop consistent with the FHL-2 form of HLH. Defective NK killing was observed for both Cryptococcus neoformans and Candida albicans. Remarkably, the defective anti-Candida activity of NK cells could be restored within 24 hours by IL-15 treatment that was similar to the enhanced anti-Candida activity of NK cells from healthy donors. We speculate that IL-15 enhances antifungal activity by stimulating NK cells to employ an alternate microbicidal effector mechanism. This result is the first to show that IL-15 can restore defective cytotoxic activity of NK cells from an HLH patient, and further studies might be considered to explore the mechanism and potential form of immunotherapy." @default.
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- W1548811214 date "2012-05-01" @default.
- W1548811214 modified "2023-09-23" @default.
- W1548811214 title "IL-15 restores defective NK anti-fungal activity in a primary Hemophagocytic lymphohistiocytosis Patient (164.1)" @default.
- W1548811214 doi "https://doi.org/10.4049/jimmunol.188.supp.164.1" @default.
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