Dynamics of thymus-colonizing cells during human development.
Here, we identify fetal bone marrow (BM)-derived CD34hiCD45RAhiCD7+ hematopoietic progenitors as thymus-colonizing cells. This population, virtually absent from the fetal liver (FL), emerges in the BM by development weeks 8-9, where it accumulates throughout the second trimester, to finally decline around birth. Based on phenotypic, molecular, and functional criteria, we demonstrate that CD34hiCD45RAhiCD7+ cells represent the direct precursors of the most immature CD34hiCD1a- fetal thymocytes that follow a similar dynamics pattern during fetal and early postnatal development. Histological analysis of fetal thymuses further reveals that early immigrants predominantly localize in the perivascular areas of the cortex, where they form a lymphostromal complex with thymic epithelial cells (TECs) driving their rapid specification toward the T lineage. Finally, using an ex vivo xenogeneic thymus-colonization assay, we show that BM-derived CD34hiCD45RAhiCD7+ progenitors are selectively recruited into the thymus parenchyma in the absence of exogenous cytokines, where they adopt a definitive T cell fate.
Laboratoire d'Immunologie Cellulaire et Immunopathologie de l'Ecole Pratique des Hautes Etudes and UMR 7151, Centre National de la Recherche Scientifique, Université Paris 7, Paris, France.
Rima
R
Haddad
Fabien
F
Guimiot
Emmanuelle
E
Six
Frederic
F
Jourquin
Niclas
N
Setterblad
Edmond
E
Kahn
Micael
M
Yagello
Cecile
C
Schiffer
Isabelle
I
Andre-Schmutz
Marina
M
Cavazzana-Calvo
Jean Claude
JC
Gluckman
Anne-Lise
AL
Delezoide
Françoise
F
Pflumio
Bruno
B
Canque
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D001853:Bone Marrow / Q000196:embryology* / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D010641:Phenotype; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology* / Q000276:immunology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte