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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2585-2593.
Prepublished online as a Blood First Edition Paper on October 7, 2004; DOI 10.1182/blood-2002-11-3463.
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Submitted December 12, 2002
Accepted October 4, 2004
Immune regulatory activity of CD34+ progenitor cells: evidence for a deletion based mechanism mediated by TNF-
Hilit Gur, Rita Krauthgamer, Esther Bachar-Lustig, Helena Katchman, Rinat Arbel-Goren, Alain Berrebi, Tirza Klein, Arnon Nagler, Antonio Tabilio, Massimo F Martelli, and Yair Reisner*
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
Department of Hematology, Kaplan Medical Center, Rehovot, Israel
Department of Tissue Typing, Rabin Medical Center, Petah Tikva, Israel
Department of Bone Marrow Transplantation, Sheba Medical Center, Tel Hashomer, Israel
Department of Hematology, University of Perugia, Perugia, Italy
* Corresponding author; email: yair.reisner{at}weizmann.ac.il.
Abstract
Previous studies suggest that cells within the CD34+ hematopoietic stem cell compartment are endowed with immune regulatory activity. Furthermore, it is possible to expand the human regulatory cells upon short-term culture of purified CD34+ cells with an early-acting cytokine cocktail. We now show that addition of anti-CD28, anti-CD2, IL-2, anti-IL-10, or IL-12 to the bulk MLR cannot reverse the inhibitory activity of the CD34+ cells, rulling out anergy based mechanisms, or mechanisms involving Th1-Th2 skewing. Furthermore, phenotyping of cells present after addition of CD34+ cells to the bulk MLR, ruled out potential induction of plasmacytoid dendritic precursors, known to be endowed with regulatory activity. In contrast, the inhibitory activity of CD34+ cells could be reversed by adding the caspase inhibitor BD-FMK to the bulk MLR, indicating a deletion based mechanism. The deletion can be inhibited by anti-TNF- and not by anti-TGF- , suggesting a potential role for TNF-a in the regulatory activity of CD34+ cells.

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