Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / physiology
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Animals
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Antibodies, Blocking / metabolism
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Antibodies, Blocking / pharmacology
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Antibodies, Monoclonal / metabolism
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Antibodies, Monoclonal / pharmacology
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Cell Differentiation / immunology
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Cell Division / immunology
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Child
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Chimera / immunology
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / immunology
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Humans
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Interleukin-9 / metabolism
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Interleukin-9 / physiology*
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Mice
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Mice, SCID
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Organ Culture Techniques
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RNA, Messenger / biosynthesis
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Receptors, Interleukin / antagonists & inhibitors
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Receptors, Interleukin / genetics
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Receptors, Interleukin / immunology
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Receptors, Interleukin / physiology*
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Receptors, Interleukin-9
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Signal Transduction / immunology*
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Thymus Gland / cytology*
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Thymus Gland / embryology*
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Thymus Gland / immunology
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Thymus Gland / metabolism
Substances
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Adjuvants, Immunologic
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Antibodies, Blocking
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Antibodies, Monoclonal
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IL9R protein, human
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Interleukin-9
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RNA, Messenger
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Receptors, Interleukin
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Receptors, Interleukin-9