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R on Bone Marrow Stromal Cells Is Required for an Early Checkpoint of NK Cell Development1
Department of
*
Pathology and
Neurology, University of Chicago, Chicago, IL 60637;
Searle Discovery, Monsanto, St. Louis, MO 63198; and
Institute of Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, Trogerstrasse, Munich, Germany
NK cells play an important role in the immune system but the
cellular and molecular requirements for their early development are
poorly understood. Lymphotoxin-
(LT)-/- and
LT
R-/- mice show a severe systemic reduction of NK
cells, which provides an excellent model to study NK cell development.
In this study, we show that the bone marrow (BM) or fetal liver cells
from LT-/- or LTR-/- mice efficiently
develop into mature NK cells in the presence of stromal cells from
wild-type mice but not from LT-/- or
LTR-/- mice. Direct activation of LTR-expressing BM
stromal cells is shown to promote to early NK cell development in
vitro. Furthermore, the blockade of the interaction between LT and
LTR in adult wild-type mice by administration of LTR-Ig impairs
the development of NK cells in vivo. Together, these results indicate
that the signal via LTR on BM stromal cells by membrane LT is an
important pathway for early NK cell development.
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