Identification of mature and immature human thymic dendritic cells that differentially express HLA-DR and interleukin-3 receptor in vivo.
We have previously shown that thymic CD34+ cells have a very limited myeloid differentiation capacity and differentiate in vitro mostly into CD1a+-derived but not CD14+-derived dendritic cells (DC). Herein we characterized the human neonatal thymic DC extracted from the organ in relationship with the DC generated from CD34+ cells in situ. We show that in vivo thymic DC express E cadherin, CLA, CD4, CD38, CD40, CD44, and granulocyte-macrophage colony-stimulating factor-R (GM-CSF-R; CD116) but no CD1a. According to their morphology, functions, and surface staining they could be separated into two distinct subpopulations: mature HLA-DRhi, mostly interleukin-3-R (CD123)-negative cells, associated with thymocytes, some apoptotic, and expressed myeloid and activation markers but no lymphoid markers. In contrast, immature HLA-DR+ CD123hi CD36+ cells with monocytoid morphology lacked activation and myeloid antigens but expressed lymphoid antigens. The latter express pTalpha mRNA, which is also found in CD34+ thymocytes and in blood CD123hi DC further linking this subset to lymphoid DC. However, the DC generated from CD34+ thymic progenitors under standard conditions were pTalpha-negative. Thymic lymphoid DC showed similar phenotype and cytokine production profile as blood/tonsillar lymphoid DC but responded to GM-CSF, and at variance with them produced no or little type I interferon upon infection with viruses and did not induce a strict polarization of naive T cells into TH2 cells. Their function in the thymus remains therefore to be elucidated.
Schmitt
C
C
UMR CNRS 7627, Hopital Pitié-Salpêtrière, Paris, France. dalloul@ccr.jussieu.fr
Fohrer
H
H
Beaudet
S
S
Palmer
P
P
Alpha
M J
MJ
Canque
B
B
Gluckman
J C
JC
Dalloul
A H
AH
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015415:Biomarkers; D015820:Cadherins / Q000032:analysis; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000737:chemistry / Q000145:classification / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D053650:Interleukin-3 Receptor alpha Subunit; D007378:Interleukins / Q000096:biosynthesis; D008222:Lymphokines / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000032:analysis; D022423:Myeloid Cells / Q000737:chemistry; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D016185:Receptors, Interleukin-3 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D018108:Respirovirus / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology*; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology
D015703:Antigens, CD; D018952:Antigens, CD34; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015415:Biomarkers; C063419:CTAGE1 protein, human; D015820:Cadherins; D006684:HLA-DR Antigens; C115022:IL3RA protein, human; D016898:Interferon-alpha; D053650:Interleukin-3 Receptor alpha Subunit; D007378:Interleukins; D008222:Lymphokines; D008562:Membrane Glycoproteins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016185:Receptors, Interleukin-3; D007371:Interferon-gamma