Identification of pro-thymocytes in murine fetal blood: T lineage commitment can precede thymus colonization.
Phenotype and commitment of thymus-colonizing precursors are unknown. Here we report the identification of T lineage-committed precursors (designated prothymocytes) in murine fetal blood at day 15.5 of development. Fetal blood pro-thymocytes are Thy-1+c-kit(low)CD3- in contrast to fetal blood-derived pluripotent hematopoietic progenitors which are Thy-1-c-kit+. Upon transfer into the thymus, fetal blood pro-thymocytes generate a single wave of CD4+CD8+ thymocytes and subsequently mature TCR alpha beta+ peripheral T cells. However, fetal blood pro-thymocytes lack multipotent progenitor potential since they fail to reconstitute B lymphocytes and myeloid and erythroid lineages. In contrast, T and B lymphocytes as well as myeloid and erythroid lineages are reconstituted from fetal blood-derived pluripotent progenitors. Pro-thymocytes are equally present in peripheral blood of athymic fetal mice, suggesting that this novel precursor population is T lineage-committed prior to thymus colonization and represents the earliest T lineage precursor identified.
Rodewald
H R
HR
Basel Institute for Immunology, Switzerland.
Kretzschmar
K
K
Takeda
S
S
Hohl
C
C
Dessing
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001483:Base Sequence; D017252:CD3 Complex / Q000032:analysis; D002454:Cell Differentiation; D005312:Fetal Blood / Q000166:cytology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016184:Receptors, Colony-Stimulating Factor / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology*; D018800:Thy-1 Antigens / Q000032:analysis; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology*
D017252:CD3 Complex; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016184:Receptors, Colony-Stimulating Factor; D018800:Thy-1 Antigens; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases