Requirement for the thymus in alphabeta T lymphocyte lineage commitment.

We recently identified a fetal thymic developmental stage (NK1.1+/CD117(lo)) that characterizes committed T/NK progenitors. We now report the existence of phenotypically and functionally identical T/NK progenitors in mouse fetal blood and spleen but not in fetal liver. These precursors are indistinguishable from previously characterized fetal blood "prothymocytes" (CD90+/CD117(lo)), with the exception that they express NK1.1, lack markers associated with T lineage commitment, maintain a germline TCRbeta locus, and can give rise to both T and NK cells. Moreover, NK1.1+/CD90+/CD117(lo) fetal blood precursors are present in athymic nude mice. These results suggest that the T/NK lineage commitment pathway is thymus-independent. In contrast, full commitment to the alphabeta T lineage does not precede thymus colonization.