title: Precursors of CD3+CD4+CD8+ cells in the human thymus are defined by expression of CD34. Delineation of early events in human thymic development.
abstract: Studies of the most immature T cell progenitors in the human thymus have been hampered by the lack of markers and assays that define these cells. In this report we used a novel human fetal thymic organ culture system to determine the potential of T cell precursors isolated from human postnatal thymus, to differentiate into CD3+ thymocytes, and to investigate early stages of human T cell development. It was found that thymocytes that lack the markers CD3, CD4, and CD8 (triple negative [TN]) can differentiate in an allogeneic organotypic thymic culture. The capacity of TN thymocytes to differentiate was exclusively confined to the CD34+ population. CD34- TN thymocytes failed to differentiate in this system. In contrast, cloned lines of CD3- thymocytes could only be established from CD34- TN thymocytes. Five subsets of CD3- thymocytes were found with the following phenotype: CD1-TN, CD1+TN, CD1+CD4+CD8-, CD1+CD4+CD8 alpha+ beta-, and CD1+CD4+CD8 alpha beta+. These subpopulations expressed decreasing levels of CD34. The CD1-CD3- population expressed the highest levels of CD34 supporting the notion that this population is the most immature T cell precursor in the thymus, whereas the CD1+CD4+CD8 alpha+ beta+ which did not express CD34 seems to be the most mature of these CD3- populations. This notion is supported by the observations that CD34+ cells isolated from fetal liver, which differentiated into T cells in a FTOC, developed into CD3+ cells via CD1- and CD4+CD8- intermediates. Based on these data, we present a model of early stages in human intrathymic development.
authors.affiliation: DNAX Research Institute, Department of Human Immunology, Palo Alto, California 94304.
authors.forename: A
authors.initials: A
authors.lastname: Galy
authors.forename: S
authors.initials: S
authors.lastname: Verma
authors.forename: A
authors.initials: A
authors.lastname: Bárcena
authors.forename: H
authors.initials: H
authors.lastname: Spits
mesh_terms: D015703:Antigens, CD; D018952:Antigens, CD34; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D002453:Cell Cycle; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007223:Infant; D008099:Liver / Q000166:cytology / Q000196:embryology; D009924:Organ Culture Techniques; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000254:growth & development
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens