IDENTIFICATION OF A NOVEL DEVELOPMENTAL STAGE MARKING LINEAGE COMMITMENT OF PROGENITOR THYMOCYTES

Bipotent progenitors for T and natural killer (NK) lymphocytes are tho ught to exist among early precursor thymocytes. The identification and functional properties of such a progenitor population remain undefine d. We report the identification of a novel developmental stage during fetal thymic ontogeny that delineates a population of T/NK-committed p rogenitors (NK1.1(+)/CD117(+)/CD44(+)/CD25(-)). Thymocytes at this sta ge in development are phenotypically and functionally distinguishable from the pool of multipotent lymphoid-restricted (B, T, and NK) precur sor thymocytes. Exposure of multipotent precursor thymocytes or fetal liver-derived hematopoietic progenitors to thymic stroma induces diffe rentiation to the bipotent developmental stage. Continued exposure to a thymic microenvironment results in predominant commitment to the T c ell lineage, whereas coculture with a bone marrow-derived stromal cell line results in the generation of mature NK cells. Thus, the restrict ion point to T and NK lymphocyte destinies from a multipotent progenit or stage is marked by a thymus-induced differentiation step.