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Interleukin-7 is a critical growth factor in early human T-cell development
J Plum, M De Smedt, G Leclercq, B Verhasselt and B Vandekerckhove
Department of Clinical Chemistry, Microbiology, and Immunology, University
Hospital of Ghent, Belgium.
Highly purified human CD34+ fetal liver stem cells differentiate to mature
T cells when seeded in vitro into isolated fetal thymic lobes of severe
combined immunodeficient (SCID) mice followed by fetal thymus organ culture
(FTOC). Here, this chimeric human-mouse FTOC was used to address the role
of interleukin-7 (IL-7) and of the alpha chain of the IL-7 receptor (IL-7R
alpha) in early human T-cell development. We report that addition of either
the monoclonal antibody (MoAb) M25, which neutralizes both human and mouse
IL-7, or the MoAb M21, which recognizes and blocks exclusively the human
high-affinity alpha-chain of the IL-7R, results in a profound reduction in
human thymic cellularity. Analysis of lymphoid subpopulations indicates
that a highly reduced number of cells undergo maturation from CD34+
precursor cells toward CD4+CD3-CD1+ progenitor cells and subsequently
toward CD4+CD8+ thymocytes. Our results reveal a critical role for IL-7
during early human thymocyte development, and may explain the absence or
highly reduced levels of T cells in patients with X-linked SCID. The
molecular defect in these patients has been shown to be a mutation in the
gamma chain of the IL-2R. Although this gamma chain is not only present in
the IL-2R, but also forms an essential part of other cytokine receptors,
including IL-4, IL-7, IL-9, IL-13, and IL-15, the T- cell defect in these
patients can be explained by the fact that IL-7 is not able to transduce
its signal by the molecular defect of the common gamma (gamma c) chain and
that IL-7 is indispensable for T-cell development.
Volume 88,
Issue 11,
pp. 4239-4245,
12/01/1996
Copyright © 1996 by The American Society of Hematology
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