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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2806-2812
Generation of T cells from adult human hematopoietic stem cells
and progenitors in a fetal thymic organ culture system: stimulation by
tumor necrosis factor-
Steven F. A. Weekx,
Hans W. Snoeck,
Fritz Offner,
Magda De Smedt,
Dirk R. Van Bockstaele,
Griet Nijs,
Marc Lenjou,
Adriaan Moulijn,
Inez Rodrigus,
Zwi N. Berneman, and
Jean Plum
From the Laboratory of Experimental Hematology and the Department of
Cardiac Surgery, University of Antwerp, Antwerp University Hospital,
Antwerp, Belgium; the Departments of Hematology and Clinical Chemistry,
Microbiology and Immunology, University of Ghent, Ghent University
Hospital, Ghent, Belgium; and the Institute for Gene Therapy and
Molecular Medicine, Mount Sinai School of Medicine, New York, NY.
To investigate the T-lymphopoietic capacity of human adult bone
marrow (ABM) hematopoietic progenitor cells, CD34+Lin ,
CD34+CD38+, and CD34++CD38 cells were cultured in a severe
combined immunodeficient (SCID) mouse fetal thymic organ culture
(FTOC). Direct seeding of these progenitors resulted in a moderate to
severe cell loss, particularly for the CD34++CD38 cell fraction,
and T cells could only be generated from the CD34+Lin fraction.
Preincubation for 36 hours with interleukin-3 (IL-3) and stem cell
factor (SCF) led to an improved cell survival and proliferation,
although T-cell development was seen only in the CD34+Lin
fraction. Addition of tumor necrosis factor (TNF)- to
IL-3 + SCF-supplemented preincubation medium resulted in optimal
cell survival, cell proliferation. and T-cell generation of all 3 cell
fractions. The TNF- effect resulted in an up-regulation of CD127
(ie, the IL-7 receptor -chain) in a small subset of the CD34+
cells. No evidence could be generated to support the possibility that
TNF- inhibits a cell population that suppresses T-cell
differentiation. A quantitatively different T-cell generation
potency was still seen between the 3 subpopulations: CD34+Lin
(100% success rate) > CD34+CD38+ (66%) > CD34++CD38 (25%). These data contrast with our previous findings using fetal liver and cord blood progenitors, which readily differentiate into
T-lymphocytes in FTOC, even without prestimulation with cytokines. Our
results demonstrate that adult CD34++CD38 cells, known to contain hematopoietic stem cells, can differentiate into T-lymphocytes and that a significant difference exists in T-lymphopoietic activity of
stem cells derived from ontogenetically different sources.
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