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Delineation of T-progenitor cell activity within the CD34+ compartment of
adult bone marrow
AH Galy, D Cen, M Travis, S Chen and BP Chen
Experimental Cellular Therapy Group, Systemix Inc, Palo Alto, CA 94304,
USA.
T-cell production is largely dependent on the presence of a thymus gland
where CD34+ precursors mature into T lymphocytes. Prethymic stages of
T-cell development are less defined. Therefore, this study aims to
delineate T-progenitor cell potential within the CD34+ Lineage-- (Lin-)
cell compartment of adult bone marrow (ABM). Fractionation of CD34+ Lin-
ABM cells with CD45RA, Thy-1, CD38, and HLA-DR failed to absolutely
segregate T-cell reconstituting ability, indicating broad distribution of
T-progenitor cell potential. Titration experiments showed that low numbers
of CD34+ Lin- CD45RA+ (RA+) cells had greater thymus repopulating ability
than CD34+ Lin- CD45RA- cells (RA-). The great majority (> 95%) of RA+
cells expressed CD38, HLA-DR and 70% to 90% of RA+ cells lacked Thy-1
surface expression. RA+ cells contained colony-forming unit
granulocyte-macrophage (CFU-GM) progenitor cells but were depleted of
erythroid potential, did not provide hematopoietic reconstitution of human
bone fragments implanted into SCID mice, and did not efficiently maintain
CD34+ cells with secondary clonogenic potential in bone marrow cultures.
Thus, RA+ cells are oligopotent (nonprimitive) CD34+ progenitors with
T-cell reconstituting ability. In contrast, these same assays indicated
that CD34+ Lin- CD45RA- cells (RA- cells) comprised hematopoietic stem
cells (HSC) with primitive multilineage (T, B, myeloid, and erythroid)
hematopoietic potential. It was confirmed that HSC-containing populations,
such as CD34+ Lin- CD45RA- Thy-1+ cells had thymus repopulating ability.
Culture of RA- cells on murine bone marrow stromal cells in the presence of
interleukin (IL)-3, IL-6, and leukemia inhibitory factor (LIF) generated
CD34+ CD45RA+ progeny engrafting in a secondary severe combined
immunodeficiency (SCID)-hu thymus assay. Altogether, our results underscore
the fact that T-cell reconstituting potential can be dissociated from HSC
activity. Furthermore, we speculate that HSC might develop into the T
lineage indirectly, via differentiation into an intermediate oligopotent
CD34+ CD45RA+ stage. Finally, T-progenitor cells can be cultured in vitro.
Volume 85,
Issue 10,
pp. 2770-2778,
05/15/1995
Copyright © 1995 by The American Society of Hematology
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