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Sequential analysis of hematopoietic reconstitution achieved by
transplantation of hematopoietic stem cells
S Okada, K Nagayoshi, H Nakauchi, S Nishikawa, Y Miura and T Suda
Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.
We confirmed that murine hematopoietic stem cells express the c-kit
molecule but not lymphohematopoietic lineage markers. These lineage
marker-negative c-kit-positive (Lin- c-kit+) cells were further divided
according to the uptake of rhodamine-123 (Rh-123). Approximately 1,000 Lin-
c-kit+ rhodamine-123dull cells, which contained 4.0 +/- 1.3 and 12.5 +/-
1.9 day 8 and day 12 spleen colony-forming units (CFU-S), respectively,
rescued the 100% of lethally irradiated mice. One third of these cells
formed colonies in the presence of interleukin-3 plus erythropoietin. The
time course of the hematopoietic reconstitution of this primitive
hematopoietic stem cell fraction was investigated by using Ly-5 congenic
mice. Although myeloid cells and B lymphocytes were detected in the
peripheral blood 2 to 3 weeks after transplantation, T lymphocytes were not
detected until 4 weeks after transplantation. It is generally assumed that
myeloid cells and B lymphocytes grow in the bone marrow and that T
lymphocytes must pass through the thymus. For the first 2 to 3 weeks after
transplantation, donor-type T lymphocytes were not dominant in the thymus,
and most donor type cells were CD4/CD8 double-negative or double-positive
(including CD4low and CD8low). Four weeks after transplantation, donor-type
T lymphocytes were dominant and the ratio of CD4/CD8 cells had recovered to
the normal pattern. However, significant numbers of T lymphocytes were
detected in the peripheral blood at this stage. Sequential analysis of
hematopoietic reconstitution from primitive stem cells demonstrates that
myeloid and B-lymphoid lineages occurred earlier than that of the
T-lymphoid lineages.
Volume 81,
Issue 7,
pp. 1720-1725,
04/01/1993
Copyright © 1993 by The American Society of Hematology
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