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Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720
NK1.1+ T cells represent a specialized T cell subset
specific for CD1d, a nonclassical MHC class I-restricting element. They
are believed to function as regulatory T cells. NK1.1+ T
cell development depends on interactions with CD1d molecules presented
by hematopoietic cells rather than thymic epithelial cells.
NK1.1+ T cells are found in the thymus as well as in
peripheral organs such as the liver, spleen, and bone marrow. The site
of development of peripheral NK1.1+ T cells is
controversial, as is the nature of the CD1d-expressing cell that
selects them. With the use of nude mice, thymectomized mice
reconstituted with fetal liver cells, and thymus-grafted mice, we
provide direct evidence that NK1.1+ T cells in the liver
are thymus dependent and can arise in the thymus from fetal liver
precursor cells. We show that the class I+
(CD1d+) cell type necessary to select NK1.1+ T
cells can originate from TCR
-/- precursors but not
from TCRß-/- precursors, indicating that the selecting
cell is a CD4+CD8+ thymocyte.
5-Bromo-2'-deoxyuridine-labeling experiments suggest that the thymic
NK1.1+ T cell population arises from proliferating
precursor cells, but is a mostly sessile population that turns over
very slowly. Since liver NK1.1+ T cells incorporate
5-bromo-2'-deoxyuridine more rapidly than thymic NK1.1+ T
cells, it appears that liver NK1.1+ T cells either
represent a subset of thymic NK1.1+ T cells or are induced
to proliferate after having left the thymus. The results indicate that
NK1.1+ T cells, like conventional T cells, arise in the
thymus where they are selected by interactions with restricting
molecules.
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R. Wang, Y. Wang-Zhu, and H. Grey Interactions between double positive thymocytes and high affinity ligands presented by cortical epithelial cells generate double negative thymocytes with T cell regulatory activity PNAS, February 19, 2002; 99(4): 2181 - 2186. [Abstract] [Full Text] [PDF]
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D. G. Pellicci, K. J.L. Hammond, A. P. Uldrich, A. G. Baxter, M. J. Smyth, and D. I. Godfrey A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1-CD4+ CD1d-dependent Precursor Stage J. Exp. Med., March 25, 2002; 195(7): 835 - 844. [Abstract] [Full Text] [PDF]
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