TY - JOUR
T1 - Differentiation of Nk1.1+, Ly49+ NK cells from flt3+ multipotent marrow progenitor cells
AU - Williams, Noelle Sevilir
AU - Klem, Jennifer
AU - Puzanov, Igor J.
AU - Sivakumar, P. V.
AU - Bennett, Michael
AU - Kumar, Vinay
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999/9/1
Y1 - 1999/9/1
N2 - To delineate factors involved in NK cell development, we established an in vitro system in which lineage marker (Lin)-, c.kit+, Sca2+ bone marrow cells differentiate into lyric NK1.1+ but Ly49- cells upon culture in IL-7, stem cell factor (SCF), and flt3 ligand (flt3L), followed by IL-15 alone. A comparison of the ability of IL-7, SCF, and flt3L to generate IL-15- responsive precursors suggested that NK progenitors express the receptor for flt3L. In support of this, when Lin-, c-kit+, flt3+ or Lin-, c-kit+, flt3- progenitors were utilized, 3-fold more NK cells arose from the flt3+ than from the flt3- progenitors. Furthermore, NK cells that arose from flt3- progenitors showed an immature NK1.1(dim), CD2-, c-kit+ phenotype as compared with the more mature NK1.1(bright), CD2(+/-), c-kit- phenotype displayed by NK cells derived from flt3+ progenitors. Both progenitors, however, gave rise to NK cells that were Ly49 negative. To test the hypothesis that additional marrow-derived signals are necessary for Ly49 expression on developing NK cells, flt3+ progenitors were grown in IL-7, SCF, and flt3L followed by culture with IL-15 and a marrow-derived stromal cell line. Expression of Ly49 molecules, including those of which the MHC class I ligands were expressed on the stromal or progenitor cells, as well as others of which the known ligands were absent, was induced within 6-13 days. Thus, we have established an in vitro system in which Ly49 expression on developing NK cells can be analyzed and possibly experimentally manipulated.
AB - To delineate factors involved in NK cell development, we established an in vitro system in which lineage marker (Lin)-, c.kit+, Sca2+ bone marrow cells differentiate into lyric NK1.1+ but Ly49- cells upon culture in IL-7, stem cell factor (SCF), and flt3 ligand (flt3L), followed by IL-15 alone. A comparison of the ability of IL-7, SCF, and flt3L to generate IL-15- responsive precursors suggested that NK progenitors express the receptor for flt3L. In support of this, when Lin-, c-kit+, flt3+ or Lin-, c-kit+, flt3- progenitors were utilized, 3-fold more NK cells arose from the flt3+ than from the flt3- progenitors. Furthermore, NK cells that arose from flt3- progenitors showed an immature NK1.1(dim), CD2-, c-kit+ phenotype as compared with the more mature NK1.1(bright), CD2(+/-), c-kit- phenotype displayed by NK cells derived from flt3+ progenitors. Both progenitors, however, gave rise to NK cells that were Ly49 negative. To test the hypothesis that additional marrow-derived signals are necessary for Ly49 expression on developing NK cells, flt3+ progenitors were grown in IL-7, SCF, and flt3L followed by culture with IL-15 and a marrow-derived stromal cell line. Expression of Ly49 molecules, including those of which the MHC class I ligands were expressed on the stromal or progenitor cells, as well as others of which the known ligands were absent, was induced within 6-13 days. Thus, we have established an in vitro system in which Ly49 expression on developing NK cells can be analyzed and possibly experimentally manipulated.
UR - http://www.scopus.com/inward/record.url?scp=0033197973&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033197973&partnerID=8YFLogxK
M3 - Article
C2 - 10453005
AN - SCOPUS:0033197973
SN - 0022-1767
VL - 163
SP - 2648
EP - 2656
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -