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

T cells and natural killer (NK) cells are presumed to share a common intrathymic precursor, The development of conventional ap 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 NE; 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 Ores. Commitment to the T/NK bipotent stage is induced by fetal thymic stroma, but is not thymus dependent, Recent data indicate that CD90(+)/CD117(lo) fetal blood prothymocytes exhibit Ng 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 die cellular and molecular events involved in fetal mouse T and NK lineage commitment and differentiation to unipotent progenitors.