Spontaneous upregulation of the CD38 expression on CD34++CD38- cells: Enhancement by interferon-γ and all-trans retinoic acid

E. Henckaerts, H. W. Snoeck, G. Nijs, M. Lenjou, I. Rodrigus, D. R. Van Bockstaelev, Z. N. Berneman

Research output: Contribution to journalArticlepeer-review

Abstract

Human hematopoietic stem cells and primitive progenitor cells are characterised by surface CD34 expression and absence of membrane CD38 expression. Upon differentiation and commitment, the expression of CD38 increases, while terminally differentiated cells are mostly CD34-CD38-. In an effort to elucidate the role of C038 in human hematopoiesis, we evaluated the regulation of the CD38 expression on human bone marrow CD34++CD38- cells by flow cytometry. After 12, 24, 48, 72 and 96 hours of incubation in a liquid culture system containing serum free medium without cytokines, the expression of CD38 was spontaneously upregulated without any sign of cell proliferation. Increasing concentrations of fetal calf serum, human serum or cord blood serum could not inhibit this spontaneous upregulation. We next tested whether transforming growth factor (TGF)- and Interferon (IFN)-y, two well known inhibitors of the proliferation and differentiation of primitive progenitor cells, could influence this spontaneous upregulation. Neither TGF-p nor IFN-y were able to maintain these cells in a CD38- state. IFN-y even potently induced a further upregulation of the expression of CD38. This effect was seen after 12 hours of culture and the CD38 expression reached its maximum after 96 hours. All-trans retinoic acid (ATRA), which is known for its induction of high levels of CD38 on HL-60 cells, enhanced the CD38 upregulation similar to what we observed with IFN-y. Cytokines known to display stimulatory effects on CD34++CD38- cells (interleukin (IL) -3, IL-1, IL-6, kit llgand, flt-3/flk-2 ligand, tumor necrosis factorex, anti-TGF- antibodies) did not influence the CD38 upregulation neither in a positive way nor in a negative way. Taken together, our data demonstrate that upon in vitro culture, even in the absence of cytokines and in serumfree media, CD34++CD38- cells lose their stem cell phenotype by spontaneous and homogeneous upregulation of CD38, an upregulation which is markedly enhanced by IFN-y and ATRA. We hypothesize that IFN-y may be an inhibitor of the proliferation of very primitive progenitor cells through enhanced and accelerated differentiation of these cells.

Original languageEnglish
Pages (from-to)796
Number of pages1
JournalExperimental Hematology
Volume25
Issue number8
StatePublished - 1997
Externally publishedYes

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