In vitro intrathymic differentiation kinetics of human fetal liver CD34+CD38- progenitors reveals a phenotypically defined dendritic/T-NK precursor split.
Human CD34+CD38- hematopoietic precursor cells from fetal liver are able to develop into T, NK, and dendritic cells in a hybrid human/mouse fetal thymic organ culture (FTOC). In this report, we pay particular attention to the early events in differentiation of these precursor cells. We show that the CD34+CD38- precursor cells, which are CD4-CD7-cyCD3-HLA-DR-/++ (cy, cytoplasmatic), differentiate into a CD4+ population that remained CD7-cyCD3-HLA-DR++ and a CD4- population that expressed CD7 and cyCD3. The CD4+CD7-cyCD3- cells differentiate into phenotypically and functionally mature dendritic cells, but do not differentiate into T or NK cells. The CD4-CD7+cyCD3+ population later differentiates into a CD4+CD7+cyCD3+HLA-DR- population, which has no potential to differentiate into dendritic cells but is able to differentiate into NK cells and gammadelta and alphabeta T lymphocytes. These findings support the notion that the T/NK split occurs downstream of the NK/dendritic split.
Plum
J
J
University of Ghent, University Hospital, Department of Clinical Chemistry, Microbiology and Immunology, Belgium. jean.plum@rug.ac.be
De Smedt
M
M
Verhasselt
B
B
Offner
F
F
Kerre
T
T
Vanhecke
D
D
Leclercq
G
G
Vandekerckhove
B
B
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000818:Animals; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005333:Fetus / Q000166:cytology / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D016513:Mice, SCID; D009244:NAD+ Nucleosidase / Q000032:analysis; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1