T cell development in PU.1-deficient mice

These studies address the role of PU.1 in T cell development through the analysis of PU.1(-/-) mice. We show that the majority of PU.1(-/-) thymocytes are blocked in differentiation prior to T cell commitment, and contain a population of thymocyte progenitors with the cell surface phenotype of CD44(+), HSA(bright), c-kit(int), Thy-1(-), CD25(-), Sca-1(-), CD4(-), and CD8(-). These cells correspond in both number and cell surface phenotype with uncommitted thymocyte progenitors found in wild-type fetal thymus, RT-PCR analysis demonstrated that PU.1 is normally expressed in this early progenitor population, but is down-regulated during T cell commitment. Rare PU.1(-/-) thymi, however, contained small numbers of thymocytes expressing markers of T cell commitment, Furthermore, almost 40% of PU.1(-/-) thymi placed in fetal thymic organ culture are capable of T cell development. Mature PU.1(-/-) thymocytes generated during organ culture proliferated and produced IL-2 in response to stimulation through the TCR, These data demonstrate that PU.1 is not absolutely required for T cell development, but does play a role in efficient commitment and/or early differentiation of most T progenitors.