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Department of Clinical Chemistry, Microbiology and Immunology, University of Ghent, University Hospital of Ghent, Ghent, Belgium; and
Ludwig Institute for Cancer Research, Brussels Branch and Experimental Medicine Unit, Catholic University of Louvain, Brussels, Belgium
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
-chain of the IL-9 receptor (IL-9R
) in
early human T cell development. We report that addition of the mAb
AH9R7, which recognizes and blocks selectively the human high affinity
-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-9R
signaling is critical in early T lymphoid
development.
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