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+, 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.

这些研究通过对PU.1基因敲除（PU.1 - / -）小鼠的分析，探讨了PU.1在T细胞发育中的作用。我们发现，大多数PU.1 - / -胸腺细胞在T细胞定向分化之前的分化过程受阻，并且包含一群具有CD44⁺、HSA明亮、c - kit中等、Thy - 1⁻、CD25⁻、Sca - 1⁻、CD4⁻和CD8⁻细胞表面表型的胸腺细胞祖细胞。这些细胞在数量和细胞表面表型上与野生型胎儿胸腺中发现的未定向胸腺细胞祖细胞相对应。逆转录 - 聚合酶链反应（RT - PCR）分析表明，PU.1在这种早期祖细胞群中正常表达，但在T细胞定向分化过程中表达下调。然而，少数PU.1 - / -胸腺含有少量表达T细胞定向分化标志物的胸腺细胞。此外，将近40%置于胎儿胸腺器官培养中的PU.1 - / -胸腺能够进行T细胞发育。在器官培养过程中产生的成熟PU.1 - / -胸腺细胞在受到T细胞受体（TCR）刺激时能够增殖并产生白细胞介素 - 2（IL - 2）。这些数据表明，PU.1对于T细胞发育并非绝对必需，但在大多数T祖细胞的有效定向分化和/或早期分化中确实起作用。