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Immune activation modulates hematopoiesis through interactions between CD27 and CD70

Abstract

The differentiation of hematopoietic stem cells into mature blood cell lineages is tightly regulated. Here we report that CD27, which is expressed on stem and early progenitor cells in bone marrow, can be important in this process. Deletion of CD27 increased the myeloid colony–forming potential of stem and early progenitor cells and enhanced B lymphoid reconstitutive capacity in competitive transplantation experiments. Conversely, stimulation of CD27+ progenitor cells with CD70, the unique ligand for CD27, inhibited colony-forming potential in vitro and lymphocyte outgrowth in vivo. As CD70 is expressed only on activated immune cells, we suggest that CD27 triggering on early progenitor cells provides a negative feedback signal to leukocyte differentiation during immune activation.

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Acknowledgements

We thank H. Hagoort and R. van Olffen for technical assistance; E. Nolte-'t Hoen (Imperial College London, London, UK), R. Mebius (VU Medical Center, Amsterdam, The Netherlands) and C. Reis e Sousa (Cancer Research UK, London, UK) for critical reading of the manuscript; and J. Borst (The Netherlands Cancer Institute, Amsterdam, The Netherlands) for providing CD27-deficient mice.

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Competing interests

The authors declare no competing financial interests.

Correspondence to René A W van Lier.

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Figure 1: CD27 expression on c-Kithi progenitor cells correlates with high colony-forming potential in vitro.
Figure 2: The absence of CD27 results in an increase in white blood cells in peripheral blood and increased myeloid colony–forming potential of bone marrow progenitor cells.
Figure 3: CD27-deficient LKS cells perform better in competitive transplantation assays than do wild-type LKS cells and give rise to more B cells.
Figure 4: In vitro differentiation in the presence of CD70-expressing cells inhibits the differentiation capacity of progenitor cells.
Figure 5: In vivo triggering of CD27 on progenitor cells with CD70 inhibits their differentiating capacity in vitro.
Figure 6: CD27 triggering hampers the repopulating ability of LKS cells in competitive transplantation assays.
Figure 7: CD27 triggering negatively influences B cell differentiation in vivo.