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Blood, 1 March 2002, Vol. 99, No. 5, pp. 1620-1626
HEMATOPOIESIS
Adapted NOD/SCID model supports development of phenotypically and
functionally mature T cells from human umbilical cord blood
CD34+ cells
Tessa C. C. Kerre,
Greet De Smet,
Magda De Smedt,
Alfred Zippelius,
Mikaël
J. Pittet,
Anton W. Langerak,
José De
Bosscher,
Fritz Offner,
Bart Vandekerckhove, and
Jean Plum
From the Department of Clinical Chemistry,
Microbiology, and Immunology and the Department of Hematology, Ghent
University Hospital, Belgium; the Division of Clinical Onco-Immunology,
Ludwig Institute for Cancer Research, University Hospital, Lausanne,
Switzerland; the Department of Immunology, University Hospital
Rotterdam, The Netherlands; and BTC Oost-Vlaanderen, Ghent, Belgium.
The NOD-LtSZ scid/scid (NOD/SCID) repopulation assay is the
criterion for the study of self-renewal and multilineage
differentiation of human hematopoietic stem cells. An important
shortcoming of this model is the reported absence of T-cell
development. We studied this aspect of the model and investigated how
it could be optimized to support T-cell development. Occasionally,
low-grade thymic engraftment was observed in NOD/SCID mice or
Rag2 / c/ mice. In
contrast, the treatment of NOD/SCID mice with a monoclonal antibody
against the murine interleukin-2R , (IL-2R) known to decrease
natural killer cell activity, resulted in human thymopoiesis in up to
60% of the mice. T-cell development was phenotypically normal and
resulted in polyclonal, mature, and functional CD1
TCR + CD4+ or CD8+
single-positive T cells. In mice with ongoing thymopoiesis, peripheral T cells were observed. TREC analysis showed that T cells with a naive
phenotype (CD45RA+) emerged from the thymus. In
approximately half of these mice, the peripheral T cells included a
pauciclonal outgrowth of CD45RO+ cells. These data
suggest that all elements of a functional immune system were present in
these animals.
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