Lineage commitment and differentiation of T and natural killer lymphocytes in the fetal mouse

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Abstract
T cells and natural killer (NK) cells are presumed to share a common intrathymic precursor. The development of conventional alpha beta T lymphocytes begins within the early fetal thymus, after the colonization of multipotent CD117+ precursors. Irrevocable commitment to the T lineage is marked by thymus-induced expression of CD25. However, the contribution of the fetal thymus to NK lineage commitment and differentiation remains largely unappreciated. Recently, we demonstrated that the development of functional mouse NK cells occurs first in the fetal thymus. Moreover, the appearance of mature fetal thymic NK cells (NK1.1+/CD117-) is preceded by a thymus-induced developmental stage (NK1.1+/CD117+) that marks lineage commitment of multipotent hematopoietic precursors to the T and NK-cell fates. Commitment to the T/NK bipotent stage is induced by fetal thymic stroma, but is not thymus dependent. Recent data indicate that CD90+/CD117lo fetal blood prothymocytes exhibit NK lineage potential and are phenotypically and functionally identical to fetal thymic NK1.1+/CD117+ progenitors. This finding also indicates that full commitment of circulating precursors to the T-cell lineage occurs after thymus colonization. In this review, we discuss recent insights into the cellular and molecular events involved in fetal mouse T and NK lineage commitment and differentiation to unipotent progenitors.