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Blood, Vol. 94 No. 7 (October 1), 1999:
pp. 2293-2300
Rapid Induction of CD40 on a Subset of Granulocyte
Colony-Stimulating Factor-Mobilized CD34+ Blood
Cells Identifies Myeloid Committed Progenitors and Permits Selection of
Nonimmunogenic CD40 Progenitor Cells
Damiano Rondelli,
Roberto M. Lemoli,
Marina Ratta,
Miriam Fogli,
Francesca Re,
Antonio Curti,
Mario Arpinati, and
Sante Tura
From the Institute of Hematology and Medical Oncology
"Seràgnoli," University of Bologna, Bologna, Italy.
CD40 antigen is a costimulatory molecule highly expressed on
dendritic cells (DC) and activated B cells, which induces T-cell proliferation through the binding with CD40L receptor. In this study,
we evaluated CD40 expression on normal CD34+
blood cells and functionally characterized
CD34+CD40+ and
CD34+CD40 cell subsets. CD40, CD80, and
CD86 antigens were constitutively expressed on 3.2% ± 4.5%, 0%,
and 1.8% ± 1.2% CD34+ blood cells, respectively.
However, after 24 hours in liquid culture with medium alone, or with
tumor-necrosis-factor- (TNF-), or with allogeneic mononuclear
cells 10.8% ± 3.8%, 75.3% ± 15.0% and 53.7% ± 17.0%
CD34+ blood cells, respectively, became
CD40+. After incubation for 24 hours with TNF-
CD34+CD40+ blood cells expressed only
myeloid markers and contained less than 5% CD86+ and
CD80+ cells. Also, a 24-hour priming with TNF- or
ligation of CD40 significantly increased the CD34+ blood
cells alloantigen presenting function. Finally, purified CD34+CD40+ blood cells stimulated an
alloreactive T-cell response in MLC, were enriched in granulocytic,
monocytic, and dendritic precursors, and generated high numbers of DC
in 11-14 d liquid cultures with GM-CSF, SCF, TNF- and FLT-3L. In
contrast, CD34+CD40 cells were poorly
immunogenic, contained committed granulocytic and erythroid precursors
and early progenitors, and differentiated poorly toward the DC lineage.
In conclusion, a short incubation with TNF- allows the selection of
CD40+ blood progenitors, which may be a useful source of
DC precursors for antitumor vaccine studies, and also a
CD34+CD40 blood cell fraction that could
be exploited in innovative strategies of allogeneic transplantation
across HLA barriers.
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