T Cell Development in PU.1-Deficient Mice

Abstract

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+, HSAbright, c-kitint, 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.