NK1.1(+) T cells in the liver arise in the thymus and are selected by interactions with class I molecules on CD4(+)CD8(+) cells

NK1.1(+) T cells represent a specialized T cell subset specific for CD1d, a nonclassical MHC class I-restricting element. They are believed to functio n as regulatory T cells. NK1.1(+) T cell development depends on interaction s with CD1d molecules presented by hematopoietic cells rather than thymic e pithelial cells. NK1.1+ T cells are found in the thymus as well as in perip heral organs such as the liver, spleen, and bone marrow. The site of develo pment 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, thym ectomized mice reconstituted with fetal liver cells, and thymus-grafted mic e, 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 alpha(-/-) precursors but not from TCR beta(-/ -) precursors, indicating that the selecting cell is a CD4(+)CD8(+) thymocy te, 5-Bromo-2'-deoxyuridine-labeling experiments suggest that the thymic NK 1.1(+) T cell population arises from proliferating precursor cells, hut 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 NR1 .1(+) T cells, it appears that liver NK1.1(+) T cells either represent a su bset 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 conventio nal T cells, arise in the thymus where they are selected by interactions wi th restricting molecules.