کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2103063 1546345 2009 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Notch Ligands Jagged2, Delta1, and Delta4 Induce Differentiation and Expansion of Functional Human NK Cells from CD34+ Cord Blood Hematopoietic Progenitor Cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
The Notch Ligands Jagged2, Delta1, and Delta4 Induce Differentiation and Expansion of Functional Human NK Cells from CD34+ Cord Blood Hematopoietic Progenitor Cells
چکیده انگلیسی

Notch receptor signaling is required for T cell development, but its role in natural killer (NK) cell development is poorly understood. We compared the ability of the 5 mammalian Notch ligands (Jagged1, Jagged2, Delta1, Delta3, or Delta4) to induce NK cell development from human hematopoietic progenitor cells (HPCs). CD34+ HPCs were cultured with OP9 stromal cell lines transduced with 1 of the Notch ligands or with OP9 stromal cells alone, in the presence of IL-7, Flt3L, and IL-15. Differentiation and expansion of CD56+CD3− cells were greatly accelerated in the presence of Jagged2, Delta-1, or Delta-4, versus culture in the absence of ligand or in the presence of Jagged1 or Delta3. At 4 weeks, cultures containing Jagged2, Delta1, or Delta4 contained 80% to 90% NK cells, with the remaining cells being CD33+ myelogenous cells. Notch-induced NK (N-NK) cells resembled CD56bright NK cells in that they were CD16−, CD94−, CD117+, and killer immunoglobulin-like receptors (KIR−). They also expressed NKp30, NKp44, NKp46, 2B4, and DNAM-1, with partial expression of NKG2D. The N-NK cells displayed cytotoxic activity against the K562 and RPMI-8226 cell lines, at levels similar to activated peripheral blood (PB) NK cells, although killing of Daudi cells was not present. N-NK cells were also capable of interferon (IFN)-γ secretion. Thus, Notch ligands have differential ability to induce and expand immature, but functional, NK cells from CD34+ HPCs. The use of Notch ligands to generate functional NK cells in vitro may be significant for cellular therapy purposes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 15, Issue 9, September 2009, Pages 1026–1037
نویسندگان
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