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ß T Cell Differentiation in Mouse Fetal Thymic Ontogeny1
Department of Immunology, University of Toronto, Toronto, Ontario, Canada
Natural killer (NK) cells mediate MHC-unrestricted cytolysis of
virus-infected cells and tumor cells. In the adult mouse, NK cells are
bone marrow-derived lymphocytes that mature predominantly in
extrathymic locations but have also been suggested to share a common
intrathymic progenitor with T lymphocytes. However, mature NK cells are
thought to be absent in mouse fetal ontogeny. We report the existence
of thymocytes with a mature NK cell phenotype
(NK1.1+/CD117-) as early as day 13 of
gestation, approximately 3 days before the appearance of
CD4+/CD8+ cells in T lymphocyte development.
These mature fetal thymic NK cells express genes associated with NK
cell effector function and, when freshly isolated, display
MHC-unrestricted cytolytic activity in vitro. Moreover, the capacity of
fetal thymic NK cells for sustained growth both in vitro and in vivo,
in addition to their close phenotypic resemblance to early precursor
thymocytes, confounds previous assessments of NK lineage precursor
function. Thus, mature NK cells may have been inadvertently included in
previous attempts to identify multipotent and bipotent precursor
thymocytes. These results provide the first evidence of functional NK
lymphocytes in mouse fetal ontogeny and demonstrate that NK cell
maturation precedes 
ß T cell development in the fetal thymus.
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