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.
Spain
L M
LM
Wistar Institute, Philadelphia, PA 19104, USA. spain@wistar.upenn.edu
Guerriero
A
A
Kunjibettu
S
S
Scott
E W
EW
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005333:Fetus; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000099232:Proto-Oncogene Protein Spi-1
D015415:Biomarkers; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1