Signals from the IL-9 receptor are critical for the early stages of human intrathymic T cell development.
Highly purified human CD34+ hemopoietic precursor cells differentiate into mature T cells when seeded in vitro in isolated fetal thymic lobes of SCID mice followed by fetal thymus organ culture (FTOC). Here, this chimeric human-mouse FTOC was used to address the role of IL-9 and of the alpha-chain of the IL-9 receptor (IL-9Ralpha) in early human T cell development. We report that addition of the mAb AH9R7, which recognizes and blocks selectively the human high affinity alpha-chain of the IL-9R, results in a profound reduction of the number of human thymocytes. Analysis of lymphoid subpopulations indicates that a highly reduced number of cells undergo maturation from CD34+ precursor cells toward CD4+CD3-CD8-CD1+ progenitor cells and subsequently toward CD4+CD8+ double positive (DP) thymocytes. Addition of IL-9 to the FTOC resulted in an increase in cell number, without disturbing the frequencies of the different subsets. These data suggest that IL-9Ralpha signaling is critical in early T lymphoid development.
De Smedt
M
M
Department of Clinical Chemistry, University of Ghent, University Hospital of Ghent, Ghent, Belgium.
Verhasselt
B
B
Kerre
T
T
Vanhecke
D
D
Naessens
E
E
Leclercq
G
G
Renauld
J C
JC
Van Snick
J
J
Plum
J
J
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002648:Child; D002678:Chimera / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D016906:Interleukin-9 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D053651:Receptors, Interleukin-9; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology* / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; C508045:IL9R protein, human; D016906:Interleukin-9; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053651:Receptors, Interleukin-9